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A Review: Molecular Chaperone-mediated Folding, Unfolding and Disaggregation of Expressed Recombinant Proteins

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Abstract

The advancements in biotechnology over time have led to an increase in the demand of pure, soluble and functionally active proteins. Recombinant protein production has thus been employed to obtain high expression of purified proteins in bulk. E. coli is considered as the most desirable host for recombinant protein production due to its inexpensive and fast cultivation, simple nutritional requirements and known genetics. Despite all these benefits, recombinant protein production often comes with drawbacks, such as, the most common being the formation of inclusion bodies due to improper protein folding. Consequently, this can lead to the loss of the structure-function relationship of a protein. Apart from various strategies, one major strategy to resolve this issue is the use of molecular chaperones that act as folding modulators for proteins. Molecular chaperones assist newly synthesized, aggregated or misfolded proteins to fold into their native conformations. Chaperones have been widely used to improve the expression of various proteins which are otherwise difficult to produce in E. coli. Here, we discuss the structure, function, and role of major E. coli molecular chaperones in recombinant technology such as trigger factor, GroEL, DnaK and ClpB.

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References

  1. Cohen, S. N., Chang, A. C. Y., Boyer, H. W., & Helling, R. B. (1973). Construction of biologically functional bacterial plasmids in vitro. Proceedings of the National Academy of Sciences of the United States of America, 70(11), 3240–3244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Itakura, K., Hirose, T., Crea, R., Riggs, A. D., Heyneker, H. L., Bolivar, F., & Boyer, H. W. (1977). Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. Science, 198(4321), 1056–1063. https://doi.org/10.1126/science.412251.

    Article  CAS  PubMed  Google Scholar 

  3. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., & Bourne, P. E. (2000). The protein data bank. Nucleic Acids Research, 28(1), 235–242. https://doi.org/10.1093/nar/28.1.235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tokmakov, A. A., Kurotani, A., Takagi, T., Toyama, M., Shirouzu, M., Fukami, Y., & Yokoyama, S. (2012). Multiple post-translational modifications affect heterologous protein synthesis. The Journal of Biological Chemistry, 287(32), 27106–27116. https://doi.org/10.1074/jbc.M112.366351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kopito, R. R. (2000). Aggresomes, inclusion bodies and protein aggregation. Trends in Cell Biology, 10(12), 524–530. https://doi.org/10.1016/S0962-8924(00)01852-3.

    Article  CAS  PubMed  Google Scholar 

  6. Rajan, R. S., Illing, M. E., Bence, N. F., & Kopito, R. R. (2001). Specificity in intracellular protein aggregation and inclusion body formation. Proceedings of the National Academy of Sciences of the United States of America, 98(23), 13060–13065. https://doi.org/10.1073/pnas.181479798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Speed, M. A., Wang, D. I. C., & King, J. (1996). Specific aggregation of partially folded polypeptide chains: The molecular basis of inclusion body composition. Nature Biotechnology, 14(10), 1283–1287. https://doi.org/10.1038/nbt1096-1283.

    Article  CAS  PubMed  Google Scholar 

  8. Lansbury, P. T. (1997). Structural neurology: are seeds at the root of neuronal degeneration? Neuron, 19(6), 1151–1154. https://doi.org/10.1016/S0896-6273(00)80406-7.

    Article  CAS  PubMed  Google Scholar 

  9. Carrió, M. M., Cubarsi, R., & Villaverde, A. (2000). Fine architecture of bacterial inclusion bodies. FEBS Letters, 471(1), 7–11. https://doi.org/10.1016/S0014-5793(00)01357-0.

    Article  PubMed  Google Scholar 

  10. Mamipour, M., Yousefi, M., & Hasanzadeh, M. (2017). An overview on molecular chaperones enhancing solubility of expressed recombinant proteins with correct folding. International Journal of Biological Macromolecules, 102, 367–375. https://doi.org/10.1016/j.ijbiomac.2017.04.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mukhopadhyay, A. (1997). Inclusion bodies and purification of proteins in biologically active forms. Biotreatment, downstream processing and modelling. https://doi.org/10.1007/BFb0103030. 61–109. Berlin, Heidelberg:Springer.

  12. Redwan, E. (2006). The optimal gene sequence for optimal protein expression in Escherichia coli: principle requirements. Oct, 9, 493–510.

    Google Scholar 

  13. Baneyx, F., & Mujacic, M. (2004). Recombinant protein folding and misfolding in Escherichia coli. Nature Biotechnology, 22(11), 1399–1408. https://doi.org/10.1038/nbt1029.

    Article  CAS  PubMed  Google Scholar 

  14. Gopal, G. J., & Kumar, A. (2013). Strategies for the production of recombinant protein in Escherichia coli. The Protein Journal, 32(6), 419–425. https://doi.org/10.1007/s10930-013-9502-5.

    Article  CAS  PubMed  Google Scholar 

  15. Rosano, G. L., & Ceccarelli, E. A. (2014). Recombinant protein expression in Escherichia coli: advances and challenges. Frontiers in Microbiology, 5. https://doi.org/10.3389/fmicb.2014.00172

  16. Sørensen, H. P., & Mortensen, K. K. (2005). Soluble expression of recombinant proteins in the cytoplasm of Escherichia coli. Microbial Cell Factories, 4(1), 1 https://doi.org/10.1186/1475-2859-4-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nguyen, H. D., Nguyen, Q. A., Ferreira, R. C., Ferreira, L. C. S., Tran, L. T., & Schumann, W. (2005). Construction of plasmid-based expression vectors for Bacillus subtilis exhibiting full structural stability. Plasmid, 54(3), 241–248. https://doi.org/10.1016/j.plasmid.2005.05.001.

    Article  CAS  PubMed  Google Scholar 

  18. Kosobokova, E. N., Skrypnik, K. A., & Kosorukov, V. S. (2016). Overview of fusion tags for recombinant proteins. Biochemistry. Biokhimiia, 81(3), 187–200. https://doi.org/10.1134/S0006297916030019.

    Article  CAS  PubMed  Google Scholar 

  19. de Marco, A. (2007). Protocol for preparing proteins with improved solubility by co-expressing with molecular chaperones in Escherichia coli. Nature Protocols, 2(10), 2632–2639. https://doi.org/10.1038/nprot.2007.400.

    Article  CAS  PubMed  Google Scholar 

  20. Villaverde, A., & Mar Carrió, M. (2003). Protein aggregation in recombinant bacteria: biological role of inclusion bodies. Biotechnology Letters, 25(17), 1385–1395. https://doi.org/10.1023/A:1025024104862.

    Article  CAS  PubMed  Google Scholar 

  21. Schlieker, C., Bukau, B., & Mogk, A. (2002). Prevention and reversion of protein aggregation by molecular chaperones in the E. coli cytosol: implications for their applicability in biotechnology. Journal of Biotechnology, 96(1), 13–21. https://doi.org/10.1016/S0168-1656(02)00033-0.

    Article  CAS  PubMed  Google Scholar 

  22. Hinault, M.-P., Ben-Zvi, A., & Goloubinoff, P. (2006). Chaperones and proteases. Journal of Molecular Neuroscience, 30(3), 249–265. https://doi.org/10.1385/JMN:30:3:249.

    Article  CAS  PubMed  Google Scholar 

  23. Priya, S., Sharma, S. K., & Goloubinoff, P. (2013). Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides. FEBS Letters, 587(13), 1981–1987. https://doi.org/10.1016/j.febslet.2013.05.014.

    Article  CAS  PubMed  Google Scholar 

  24. Meimaridou, E., Gooljar, S. B., & Chapple, J. P. (2009). From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. Journal of Molecular Endocrinology, 42(1), 1–9. https://doi.org/10.1677/JME-08-0116.

    Article  CAS  PubMed  Google Scholar 

  25. Díaz-Villanueva, J. F., Díaz-Molina, R., & García-González, V. (2015). Protein folding and mechanisms of proteostasis. International Journal of Molecular Sciences, 16(8), 17193. https://doi.org/10.3390/ijms160817193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Veinger, L., Diamant, S., Buchner, J., & Goloubinoff, P. (1998). The small heat-shock protein IbpB from Escherichia coli stabilizes stress-denatured proteins for subsequent refolding by a multichaperone network. Journal of Biological Chemistry, 273(18), 11032–11037. https://doi.org/10.1074/jbc.273.18.11032.

    Article  CAS  Google Scholar 

  27. Mróz, D., Wyszkowski, H., Szablewski, T., Zawieracz, K., Dutkiewicz, R., Bury, K., & Zietkiewicz, S. (2020). CLPB (caseinolytic peptidase B homolog), the first mitochondrial protein refoldase associated with human disease. Biochimica et Biophysica Acta (BBA) - General Subjects, 1864(4), 129512 https://doi.org/10.1016/j.bbagen.2020.129512.

    Article  CAS  Google Scholar 

  28. Waters, E. R., Lee, G. J., & Vierling, E. (1996). Evolution, structure and function of the small heat shock proteins in plants. Journal of Experimental Botany, 47(3), 325–338. https://doi.org/10.1093/jxb/47.3.325.

    Article  CAS  Google Scholar 

  29. Bhandari, V., & Houry, W. A. In: P. Krogan, J. Nevan, P. Babu. Mohan, (eds.) (2015). Substrate interaction networks of the Escherichia coli Chaperones: Trigger Factor, DnaK and GroEL. Prokaryotic Systems Biology. https://doi.org/10.1007/978-3-319-23603-2_15. 271–294. Cham: Springer International Publishing. .

  30. Hartl, F. U., & Hayer-Hartl, M. (2002). Molecular chaperones in the cytosol: from nascent chain to folded protein. Science, 295(5561), 1852–1858. https://doi.org/10.1126/science.1068408.

    Article  CAS  PubMed  Google Scholar 

  31. Mayer, M. P., & Bukau, B. (2005). Hsp70 chaperones: cellular functions and molecular mechanism. Cellular and Molecular Life Sciences, 62(6), 670 https://doi.org/10.1007/s00018-004-4464-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dwivedi, P., Rodriguez, J., Ibe, N. U., & Weers, P. M. M. (2016). Deletion of the N- or C-terminal helix of apolipophorin III to create a four-helix bundle protein. Biochemistry, 55(26), 3607–3615. https://doi.org/10.1021/acs.biochem.6b00381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Braig, K. (1998). Chaperonins. Current opinion in structural biology, 8(2), 159–165.

    Article  CAS  PubMed  Google Scholar 

  34. Gupta, R. S. (1995). Evolution of the chaperonin families (HSP60, HSP 10 and TCP-1) of proteins and the origin of eukaryotic cells. Molecular microbiology, 15(1), 1–11.

    Article  CAS  PubMed  Google Scholar 

  35. Bult, C. J., White, O., Olsen, G. J., Zhou, L., Fleischmann, R. D., Sutton, G. G., & Gocayne, J. D. (1996). Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science, 273(5278), 1058–1073.

    Article  CAS  PubMed  Google Scholar 

  36. Leroux, M. R., & Hartl, F. U. (2000). Protein folding: versatility of the cytosolic chaperonin TRiC/CCT. Current Biology, 10(7), R260–R264.

    Article  CAS  PubMed  Google Scholar 

  37. Meyer, A. S., Gillespie, J. R., Walther, D., Millet, I. S., Doniach, S., & Frydman, J. (2003). Closing the folding chamber of the eukaryotic chaperonin requires the transition state of ATP hydrolysis. Cell, 113(3), 369–381.

    Article  CAS  PubMed  Google Scholar 

  38. Gutsche, I., Essen, L.-O., & Baumeister, W. (1999). Group II chaperonins: new TRiC (k) s and turns of a protein folding machine. Journal of molecular biology, 293(2), 295–312.

    Article  CAS  PubMed  Google Scholar 

  39. Carrascosa, J. L., Llorca, O., & Valpuesta, J. M. (2001). Structural comparison of prokaryotic and eukaryotic chaperonins. Micron, 32(1), 43–50.

    Article  CAS  PubMed  Google Scholar 

  40. Kubota, H., Hynes, G., Carne, A., Ashworth, A., & Willison, K. (1994). Identification of six Tcp-1-related genes encoding divergent subunits of the TCP-1-containing chaperonin. Current Biology, 4(2), 89–99.

    Article  CAS  PubMed  Google Scholar 

  41. Jacob, E., Horovitz, A., & Unger, R. (2007). Different mechanistic requirements for prokaryotic and eukaryotic chaperonins: a lattice study. Bioinformatics, 23(13), i240–i248. https://doi.org/10.1093/bioinformatics/btm180.

    Article  CAS  PubMed  Google Scholar 

  42. Ma, J., Sigler, P. B., Xu, Z., & Karplus, M. (2000). A dynamic model for the allosteric mechanism of GroEL. Journal of Molecular Biology, 302(2), 303–313.

    Article  CAS  PubMed  Google Scholar 

  43. Yifrach, O., & Horovitz, A. (1998). Mapping the transition state of the allosteric pathway of GroEL by protein engineering. Journal of the American Chemical Society, 120(50), 13262–13263.

    Article  CAS  Google Scholar 

  44. Rivenzon-Segal, D., Wolf, S. G., Shimon, L., Willison, K. R., & Horovitz, A. (2005). Sequential ATP-induced allosteric transitions of the cytoplasmic chaperonin containing TCP-1 revealed by EM analysis. Nature Structural & Molecular Biology, 12(3), 233–237.

    Article  CAS  Google Scholar 

  45. Frydman, J. (2001). Folding of newly translated proteins in vivo: the role of molecular chaperones. Annual Review of Biochemistry, 70(1), 603–647.

    Article  CAS  PubMed  Google Scholar 

  46. McCarty, J. S., Buchberger, A., Reinstein, J., & Bukau, B. (1995). The role of ATP in the functional cycle of the DnaK chaperone system. Journal of Molecular Biology, 249(1), 126–137.

    Article  CAS  PubMed  Google Scholar 

  47. Minami, Y., Höhfeld, J., Ohtsuka, K., & Hartl, F.-U. (1996). Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40. Journal of Biological Chemistry, 271(32), 19617–19624.

    Article  CAS  Google Scholar 

  48. Ziegelhoffer, T., Lopez-Buesa, P., & Craig, E. A. (1995). The dissociation of ATP from hsp70 of Saccharomyces cerevisiae is stimulated by both Ydj1p and peptide substrates. Journal of Biological Chemistry, 270(18), 10412–10419.

    Article  CAS  Google Scholar 

  49. Alibol, M. I., Mirzahoseini, H., Nehi, F. M., Tabatabaian, G., Amini, H., & Sardari, S. (2010). Improving recombinant protein solubility in Escherichia coli: Identification of best chaperone combination which assists folding of human basic fibroblast growth factor. African Journal of Biotechnology, 9(47), 8100–8109. https://doi.org/10.5897/AJB10.867.

    Article  Google Scholar 

  50. Kramer, G., Rutkowska, A., Wegrzyn, R. D., Patzelt, H., Kurz, T. A., Merz, F., & Bukau, B. (2004). Functional dissection of Escherichia coli trigger factor: unraveling the function of individual domains. Journal of Bacteriology, 186(12), 3777–3784. https://doi.org/10.1128/JB.186.12.3777-3784.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Agashe, V. R., Guha, S., Chang, H.-C., Genevaux, P., Hayer-Hartl, M., Stemp, M., & Barral, J. M. (2004). Function of trigger factor and DnaK in multidomain protein folding: increase in yield at the expense of folding speed. Cell, 117(2), 199–209. https://doi.org/10.1016/s0092-8674(04)00299-5.

    Article  CAS  PubMed  Google Scholar 

  52. Deuerling, E., Schulze-Specking, A., Tomoyasu, T., Mogk, A., & Bukau, B. (1999). Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature, 400(6745), 693–696. https://doi.org/10.1038/23301.

    Article  CAS  PubMed  Google Scholar 

  53. Makhoba, X. H., Pooe, O. J., & Mthembu, M. S. (2015). Molecular chaperone assisted expression systems: obtaining pure soluble and active recombinant proteins for structural and therapeutic purposes. https://doi.org/10.4172/jpb.1000371.

  54. Ratelade, J., Miot, M.-C., Johnson, E., Betton, J.-M., Mazodier, P., & Benaroudj, N. (2009). Production of recombinant proteins in the lon-deficient BL21(DE3) strain of Escherichia coli in the absence of the DnaK chaperone. Applied and Environmental Microbiology, 75(11), 3803–3807. https://doi.org/10.1128/AEM.00255-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Craig, E. A., Eisenman, H. C., & Hundley, H. A. (2003). Ribosome-tethered molecular chaperones: the first line of defense against protein misfolding? Current Opinion in Microbiology, 6(2), 157–162. https://doi.org/10.1016/s1369-5274(03)00030-4.

    Article  CAS  PubMed  Google Scholar 

  56. Wegrzyn, R. D., & Deuerling, E. (2005). Molecular guardians for newborn proteins: ribosome-associated chaperones and their role in protein folding. Cellular and molecular life sciences: CMLS, 62(23), 2727–2738. https://doi.org/10.1007/s00018-005-5292-z.

    Article  CAS  PubMed  Google Scholar 

  57. Crooke, E., Guthrie, B., Lecker, S., Lill, R., & Wickner, W. (1988). ProOmpA is stabilized for membrane translocation by either purified E. coli trigger factor or canine signal recognition particle. Cell, 54(7), 1003–1011. https://doi.org/10.1016/0092-8674(88)90115-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kaiser, C. M., Chang, H.-C., Agashe, V. R., Lakshmipathy, S. K., Etchells, S. A., Hayer-Hartl, M., & Barral, J. M. (2006). Real-time observation of trigger factor function on translating ribosomes. Nature, 444(7118), 455–460. https://doi.org/10.1038/nature05225.

    Article  CAS  PubMed  Google Scholar 

  59. Vorderwülbecke, S., Kramer, G., Merz, F., Kurz, T. A., Rauch, T., Zachmann-Brand, B., & Deuerling, E. (2004). Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor and DnaK. FEBS Letters, 559(1–3), 181–187. https://doi.org/10.1016/S0014-5793(04)00052-3.

    Article  CAS  PubMed  Google Scholar 

  60. Ferbitz, L., Maier, T., Patzelt, H., Bukau, B., Deuerling, E., & Ban, N. (2004). Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins. Nature, 431(7008), 590–596. https://doi.org/10.1038/nature02899.

    Article  CAS  PubMed  Google Scholar 

  61. Schlünzen, F., Wilson, D. N., Tian, P., Harms, J. M., McInnes, S. J., Hansen, H. A. S., & Fucini, P. (2005). The binding mode of the trigger factor on the Ribosome: implications for protein folding and SRP interaction. Structure, 13(11), 1685–1694. https://doi.org/10.1016/j.str.2005.08.007.

    Article  CAS  PubMed  Google Scholar 

  62. Kramer, G., Rauch, T., Rist, W., Vorderwülbecke, S., Patzelt, H., Schulze-Specking, A., & Bukau, B. (2002). L23 protein functions as a chaperone docking site on the ribosome. Nature, 419(6903), 171–174. https://doi.org/10.1038/nature01047.

    Article  CAS  PubMed  Google Scholar 

  63. Hesterkamp, T., Deuerling, E., & Bukau, B. (1997). The amino-terminal 118 amino acids of Escherichia coli trigger factor constitute a domain that is necessary and sufficient for binding to ribosomes. Journal of Biological Chemistry, 272(35), 21865–21871. https://doi.org/10.1074/jbc.272.35.21865.

    Article  CAS  Google Scholar 

  64. Merz, F., Hoffmann, A., Rutkowska, A., Zachmann-Brand, B., Bukau, B., & Deuerling, E. (2006). The C-terminal domain of escherichia coli trigger factor represents the central module of its chaperone activity. Journal of Biological Chemistry, 281(42), 31963–31971. https://doi.org/10.1074/jbc.M605164200.

    Article  CAS  Google Scholar 

  65. Li, Z., Wu, D., Zhan, B., Hu, X., Gan, J., Ji, C., & Li, J. (2019). Structural insights into the complex of trigger factor chaperone and ribosomal protein S7 from Mycobacterium tuberculosis. Biochemical and Biophysical Research Communications, 512(4), 838–844. https://doi.org/10.1016/j.bbrc.2019.03.166.

    Article  CAS  PubMed  Google Scholar 

  66. Kramer, G., Patzelt, H., Rauch, T., Kurz, T. A., Vorderwülbecke, S., Bukau, B., & Deuerling, E. (2004). Trigger factor peptidyl-prolyl cis/trans isomerase activity is not essential for the folding of cytosolic proteins in Escherichia coli. The Journal of Biological Chemistry, 279(14), 14165–14170. https://doi.org/10.1074/jbc.M313635200.

    Article  CAS  PubMed  Google Scholar 

  67. Kawagoe, S., Nakagawa, H., Kumeta, H., Ishimori, K., & Saio, T. (2018). Structural insight into proline cis/trans isomerization of unfolded proteins catalyzed by the trigger factor chaperone. The Journal of Biological Chemistry, 293(39), 15095–15106. https://doi.org/10.1074/jbc.RA118.003579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Baram, D., Pyetan, E., Sittner, A., Auerbach-Nevo, T., Bashan, A., & Yonath, A. (2005). Structure of trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action. Proceedings of the National Academy of Sciences, 102(34), 12017–12022.

    Article  CAS  Google Scholar 

  69. Bingel-Erlenmeyer, R., Kohler, R., Kramer, G., Sandikci, A., Antolic, S., Maier, T., & Ban, N. (2008). A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing. Nature, 452(7183), 108–111. https://doi.org/10.1038/nature06683.

    Article  CAS  PubMed  Google Scholar 

  70. Zeng, L.-L., Yu, L., Li, Z.-Y., Perrett, S., & Zhou, J.-M. (2006). Effect of C-terminal truncation on the molecular chaperone function and dimerization of Escherichia coli trigger factor. Biochimie, 88(6), 613–619.

    Article  CAS  PubMed  Google Scholar 

  71. Martinez-Hackert, E., & Hendrickson, W. A. (2009). Promiscuous substrate recognition in folding and assembly activities of the trigger factor chaperone. Cell, 138(5), 923–934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hoffmann, A., Bukau, B., & Kramer, G. (2010). Structure and function of the molecular chaperone Trigger Factor. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1803(6), 650–661. https://doi.org/10.1016/j.bbamcr.2010.01.017.

    Article  CAS  Google Scholar 

  73. Yao, Y., Bhabha, G., Kroon, G., Landes, M., & Dyson, H. J. (2008). Structure discrimination for the C-terminal domain of Escherichia coli trigger factor in solution. Journal of Biomolecular NMR, 40(1), 23–30.

    Article  CAS  PubMed  Google Scholar 

  74. Saio, T., Guan, X., Rossi, P., Economou, A., & Kalodimos, C. G. (2014). Structural basis for protein antiaggregation activity of the trigger factor chaperone. Science (New York, N.Y.), 344(6184), 1250494 https://doi.org/10.1126/science.1250494.

    Article  CAS  Google Scholar 

  75. Fayet, O., Ziegelhoffer, T., & Georgopoulos, C. (1989). The groES and groEL heat shock gene products of Escherichia coli are essential for bacterial growth at all temperatures. Journal of Bacteriology, 171(3), 1379–1385. https://doi.org/10.1128/jb.171.3.1379-1385.1989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kerner, M. J., Naylor, D. J., Ishihama, Y., Maier, T., Chang, H.-C., Stines, A. P., & Hartl, F. U. (2005). Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli. Cell, 122(2), 209–220. https://doi.org/10.1016/j.cell.2005.05.028.

    Article  CAS  PubMed  Google Scholar 

  77. Georgopoulos, C. P., Hendrix, R. W., Casjens, S. R., & Kaiser, A. D. (1973). Host participation in bacteriophage lambda head assembly. Journal of Molecular Biology, 76(1), 45–60. https://doi.org/10.1016/0022-2836(73)90080-6.

    Article  CAS  PubMed  Google Scholar 

  78. Lin, Z., & Rye, H. S. (2006). GroEL-mediated protein folding: making the impossible, possible. Critical Reviews in Biochemistry and Molecular Biology, 41(4), 211–239. https://doi.org/10.1080/10409230600760382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Herendeen, S. L., VanBogelen, R. A., & Neidhardt, F. C. (1979). Levels of major proteins of Escherichia coli during growth at different temperatures. Journal of Bacteriology, 139(1), 185–194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Horwich, A. L., Low, K. B., Fenton, W. A., Hirshfield, I. N., & Furtak, K. (1993). Folding in vivo of bacterial cytoplasmic proteins: role of GroEL. Cell, 74(5), 909–917. https://doi.org/10.1016/0092-8674(93)90470-b.

    Article  CAS  PubMed  Google Scholar 

  81. Ewalt, K. L., Hendrick, J. P., Houry, W. A., & Hartl, F. U. (1997). In vivo observation of polypeptide flux through the bacterial chaperonin system. Cell, 90(3), 491–500. https://doi.org/10.1016/s0092-8674(00)80509-7.

    Article  CAS  PubMed  Google Scholar 

  82. Fujiwara, K., Ishihama, Y., Nakahigashi, K., Soga, T., & Taguchi, H. (2010). A systematic survey of in vivo obligate chaperonin-dependent substrates. The EMBO Journal, 29(9), 1552–1564. https://doi.org/10.1038/emboj.2010.52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Niwa, T., Fujiwara, K., & Taguchi, H. (2016). Identification of novel in vivo obligate GroEL/ES substrates based on data from a cell-free proteomics approach. FEBS Letters, 590(2), 251–257. https://doi.org/10.1002/1873-3468.12036.

    Article  CAS  PubMed  Google Scholar 

  84. Braig, K., Otwinowski, Z., Hegde, R., Boisvert, D. C., Joachimiak, A., Horwich, A. L., & Sigler, P. B. (1994). The crystal structure of the bacterial chaperonin GroEL at 2.8 A. Nature, 371(6498), 578–586. https://doi.org/10.1038/371578a0.

    Article  CAS  PubMed  Google Scholar 

  85. Saibil, H. R., Fenton, W. A., Clare, D. K., & Horwich, A. L. (2013). Structure and allostery of the Chaperonin GroEL. Journal of Molecular Biology, 425(9), 1476–1487. https://doi.org/10.1016/j.jmb.2012.11.028.

    Article  CAS  PubMed  Google Scholar 

  86. Hartl, F. U., & Hayer-Hartl, M. (2009). Converging concepts of protein folding in vitro and in vivo. Nature Structural & Molecular Biology, 16(6), 574–581. https://doi.org/10.1038/nsmb.1591.

    Article  CAS  Google Scholar 

  87. Sigler, P. B., Xu, Z., Rye, H. S., Burston, S. G., Fenton, W. A., & Horwich, A. L. (1998). Structure and function in GroEL-mediated protein folding. Annual Review of Biochemistry, 67(1), 581–608. https://doi.org/10.1146/annurev.biochem.67.1.581.

    Article  CAS  PubMed  Google Scholar 

  88. Landry, S. J., Taher, A., Georgopoulos, C., & Van Der Vies, S. M. (1996). Interplay of structure and disorder in Cochaperonin mobile loops. Proceedings of the National Academy of Sciences of the United States of America, 93(21), 11622–11627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Fenton, W. A., Kashi, Y., Furtak, K., & Horwich, A. L. (1994). Residues in chaperonin GroEL required for polypeptide binding and release. Nature, 371(6498), 614–619. https://doi.org/10.1038/371614a0.

    Article  CAS  PubMed  Google Scholar 

  90. Xu, Z., Horwich, A. L., & Sigler, P. B. (1997). The crystal structure of the asymmetric GroEL–GroES–(ADP) 7 chaperonin complex. Nature, 388(6644), 741–750. https://doi.org/10.1038/41944.

    Article  CAS  PubMed  Google Scholar 

  91. Hunt, J. F., Weaver, A. J., Landry, S. J., Gierasch, L., & Deisenhofer, J. (1996). The crystal structure of the GroES co-chaperonin at 2.8 A resolution. Nature, 379(6560), 37–45. https://doi.org/10.1038/379037a0.

    Article  CAS  PubMed  Google Scholar 

  92. Ranson, N. A., Clare, D. K., Farr, G. W., Houldershaw, D., Horwich, A. L., & Saibil, H. R. (2006). Allosteric signaling of ATP hydrolysis in GroEL-GroES complexes. Nature Structural & Molecular Biology, 13(2), 147–152. https://doi.org/10.1038/nsmb1046.

    Article  CAS  Google Scholar 

  93. Gross, M., Robinson, C. V., Mayhew, M., Hartl, F. U., & Radford, S. E. (1996). Significant hydrogen exchange protection in GroEL-bound DHFR is maintained during iterative rounds of substrate cycling. Protein Science: A Publication of the Protein Society, 5(12), 2506–2513. https://doi.org/10.1002/pro.5560051213.

    Article  CAS  Google Scholar 

  94. Bukau, B., & Horwich, A. L. (1998). The Hsp70 and Hsp60 chaperone machines. Cell, 92(3), 351–366.

    Article  CAS  PubMed  Google Scholar 

  95. Powers, E. T., & Balch, W. E. (2013). Diversity in the origins of proteostasis networks—a driver for protein function in evolution. Nature Reviews Molecular Cell Biology, 14(4), 237–248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kim, Y. E., Hipp, M. S., Bracher, A., Hayer-Hartl, M., & Ulrich Hartl, F. (2013). Molecular chaperone functions in protein folding and proteostasis. Annual Review of Biochemistry, 82, 323–355.

    Article  CAS  PubMed  Google Scholar 

  97. Zuiderweg, E. R., Bertelsen, E. B., Rousaki, A., Mayer, M. P., Gestwicki, J. E., & Ahmad, A. (2012). Allostery in the Hsp70 chaperone proteins. Topics in Current Chemistry, 328, 99–153. https://doi.org/10.1007/128_2012_323.

    Article  CAS  Google Scholar 

  98. Calloni, G., Chen, T., Schermann, S. M., Chang, H., Genevaux, P., Agostini, F., & Hartl, F. U. (2012). DnaK functions as a central hub in the E. coli chaperone network. Cell Reports, 1(3), 251–264.

    Article  CAS  PubMed  Google Scholar 

  99. Liberek, K., Marszalek, J., Ang, D., Georgopoulos, C., & Zylicz, M. (1991). Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proceedings of the National Academy of Sciences, 88(7), 2874–2878.

    Article  CAS  Google Scholar 

  100. Bukau, B., & Walker, G. C. (1989). Cellular defects caused by deletion of the Escherichia coli dnaK gene indicate roles for heat shock protein in normal metabolism. Journal of Bacteriology, 171(5), 2337–2346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Melero, R., Moro, F., Pérez-Calvo, M. Á., Perales-Calvo, J., Quintana-Gallardo, L., Llorca, O., & Valpuesta, J. M. (2015). Modulation of the chaperone DnaK allosterism by the nucleotide exchange factor GrpE. Journal of Biological Chemistry, 290(16), 10083–10092.

    Article  CAS  Google Scholar 

  102. Bukau, B., Weissman, J., & Horwich, A. (2006). Molecular chaperones and protein quality control. Cell, 125(3), 443–451.

    Article  CAS  PubMed  Google Scholar 

  103. Young, J. C. (2010). Mechanisms of the Hsp70 chaperone system. Biochemistry and Cell Biology = Biochimie et biologie cellulaire, 88(2), 291–300. https://doi.org/10.1139/o09-175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Bauer, D., Merz, D. R., Pelz, B., Theisen, K. E., Yacyshyn, G., Mokranjac, D., & Žoldák, G. (2015). Nucleotides regulate the mechanical hierarchy between subdomains of the nucleotide binding domain of the Hsp70 chaperone DnaK. Proceedings of the National Academy of Sciences, 112(33), 10389–10394.

    Article  CAS  Google Scholar 

  105. Swain, J. F., Dinler, G., Sivendran, R., Montgomery, D. L., Stotz, M., & Gierasch, L. M. (2007). Hsp70 chaperone ligands control domain association via an allosteric mechanism mediated by the interdomain linker. Molecular Cell, 26(1), 27–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Vogel, M., Mayer, M. P., & Bukau, B. (2006). Allosteric regulation of Hsp70 chaperones involves a conserved interdomain linker. Journal of Biological Chemistry, 281(50), 38705–38711.

    Article  CAS  Google Scholar 

  107. Schlecht, R., Erbse, A. H., Bukau, B., & Mayer, M. P. (2011). Mechanics of Hsp70 chaperones enables differential interaction with client proteins. Nature structural & molecular biology, 18(3), 345.

    Article  CAS  Google Scholar 

  108. Sarbeng, E. B., Liu, Q., Tian, X., Yang, J., Li, H., Wong, J. L., & Liu, Q. (2015). A functional DnaK dimer is essential for the efficient interaction with Hsp40 heat shock protein. Journal of Biological Chemistry, 290(14), 8849–8862.

    Article  CAS  Google Scholar 

  109. Rüdiger, S., Buchberger, A., & Bukau, B. (1997). Interaction of Hsp70 chaperones with substrates. Nature Structural Biology, 4(5), 342–349.

    Article  PubMed  Google Scholar 

  110. Zhu, X., Zhao, X., Burkholder, W. F., Gragerov, A., Ogata, C. M., Gottesman, M. E., & Hendrickson, W. A. (1996). Structural analysis of substrate binding by the molecular chaperone DnaK. Science, 272(5268), 1606–1614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zhuravleva, A., & Gierasch, L. M. (2011). Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones. Proceedings of the National Academy of Sciences, 108(17), 6987–6992. https://doi.org/10.1073/pnas.1014448108.

    Article  Google Scholar 

  112. Mayer, M. P. (2018). Intra-molecular pathways of allosteric control in Hsp70s. Philosophical Transactions of the Royal Society B: Biological Sciences, 373(1749), 20170183.

    Article  Google Scholar 

  113. Walsh, P., Bursac, D., Law, Y. C., Cyr, D., & Lithgow, T. (2004). The J-protein family: modulating protein assembly, disassembly and translocation. EMBO reports, 5(6), 567–571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kampinga, H. H., & Craig, E. A. (2010). The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nature Reviews Molecular Cell Biology, 11(8), 579–592. https://doi.org/10.1038/nrm2941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Kabani, M. (2009). Structural and functional diversity among eukaryotic Hsp70 nucleotide exchange factors. Protein and Peptide Letters, 16(6), 623–630.

    Article  CAS  PubMed  Google Scholar 

  116. Nakazaki, Y., & Watanabe, Y.-H. (2014). ClpB chaperone passively threads soluble denatured proteins through its central pore. Genes to Cells, 19(12), 891–900. https://doi.org/10.1111/gtc.12188.

    Article  CAS  PubMed  Google Scholar 

  117. Ranaweera, C. B., Glaza, P., Yang, T., & Zolkiewski, M. (2018). Interaction of substrate-mimicking peptides with the AAA+ ATPase ClpB from Escherichia coli. Archives of Biochemistry and Biophysics, 655, 12–17. https://doi.org/10.1016/j.abb.2018.08.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Doyle, S. M., Genest, O., & Wickner, S. (2013). Protein rescue from aggregates by powerful molecular chaperone machines. Nature Reviews Molecular Cell Biology, 14(10), 617–629. https://doi.org/10.1038/nrm3660.

    Article  CAS  PubMed  Google Scholar 

  119. Weibezahn, J., Tessarz, P., Schlieker, C., Zahn, R., Maglica, Z., Lee, S., & Bukau, B. (2004). Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB. Cell, 119(5), 653–665. https://doi.org/10.1016/j.cell.2004.11.027.

    Article  CAS  PubMed  Google Scholar 

  120. Rosenzweig, R., Farber, P., Velyvis, A., Rennella, E., Latham, M. P., & Kay, L. E. (2015). ClpB N-terminal domain plays a regulatory role in protein disaggregation. Proceedings of the National Academy of Sciences, 112(50), E6872–E6881. https://doi.org/10.1073/pnas.1512783112.

    Article  CAS  Google Scholar 

  121. Durie, C. L., Duran, E. C., & Lucius, A. L. (2018). Escherichia coli DnaK allosterically modulates ClpB between high- and low-peptide affinity states. Biochemistry, 57(26), 3665–3675. https://doi.org/10.1021/acs.biochem.8b00045.

    Article  CAS  PubMed  Google Scholar 

  122. Alam, A., Golovliov, I., Javed, E., Kumar, R., Ådén, J., & Sjöstedt, A. (2020). Dissociation between the critical role of ClpB of Francisella tularensis for the heat shock response and the DnaK interaction and its important role for efficient type VI secretion and bacterial virulence. PLOS Pathogens, 16(4), e1008466 https://doi.org/10.1371/journal.ppat.1008466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Li, T., Lin, J., & Lucius, A. L. (2015). Examination of polypeptide substrate specificity for E scherichia coli C lp B. Proteins: Structure, Function, and Bioinformatics, 83(1), 117–134.

    Article  CAS  Google Scholar 

  124. Li, T., Weaver, C. L., Lin, J., Duran, E. C., Miller, J. M., & Lucius, A. L. (2015). Escherichia coli ClpB is a non-processive polypeptide translocase. Biochemical Journal, 470(1), 39–52. https://doi.org/10.1042/BJ20141457.

    Article  CAS  PubMed Central  Google Scholar 

  125. Lee, S., Sowa, M. E., Watanabe, Y., Sigler, P. B., Chiu, W., Yoshida, M., & Tsai, F. T. F. (2003). The structure of ClpB: a molecular chaperone that rescues proteins from an aggregated state. Cell, 115(2), 229–240. https://doi.org/10.1016/S0092-8674(03)00807-9.

    Article  CAS  PubMed  Google Scholar 

  126. Rosenzweig, R., Moradi, S., Zarrine-Afsar, A., Glover, J. R., & Kay, L. E. (2013). Unraveling the mechanism of protein disaggregation through a ClpB-DnaK interaction. Science, 339(6123), 1080–1083. https://doi.org/10.1126/science.1233066.

    Article  CAS  PubMed  Google Scholar 

  127. Seyffer, F., Kummer, E., Oguchi, Y., Winkler, J., Kumar, M., Zahn, R., & Mogk, A. (2012). Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces. Nature Structural & Molecular Biology, 19(12), 1347–1355. https://doi.org/10.1038/nsmb.2442.

    Article  CAS  Google Scholar 

  128. Barnett, M. E., Nagy, M., Kedzierska, S., & Zolkiewski, M. (2005). The amino-terminal domain of ClpB supports binding to strongly aggregated proteins. Journal of Biological Chemistry, 280(41), 34940–34945. https://doi.org/10.1074/jbc.M505653200.

    Article  CAS  Google Scholar 

  129. Mizuno, S., Nakazaki, Y., Yoshida, M., & Watanabe, Y. (2012). Orientation of the amino-terminal domain of ClpB affects the disaggregation of the protein. The FEBS Journal, 279(8), 1474–1484. https://doi.org/10.1111/j.1742-4658.2012.08540.x.

    Article  CAS  PubMed  Google Scholar 

  130. Ranaweera, C. B., Glaza, P., Yang, T., & Zolkiewski, M. (2018). Interaction of substrate-mimicking peptides with the AAA+ ATPase ClpB from Escherichia coli. Archives of Biochemistry and Biophysics, 655, 12–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Johnston, D. M., Miot, M., Hoskins, J. R., Wickner, S., & Doyle, S. M. (2017). Substrate discrimination by ClpB and Hsp104. Frontiers in Molecular Biosciences, 4, 36.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Lee, J., Kim, J.-H., Biter, A. B., Sielaff, B., Lee, S., & Tsai, F. T. F. (2013). Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor. Proceedings of the National Academy of Sciences, 110(21), 8513–8518. https://doi.org/10.1073/pnas.1217988110.

    Article  Google Scholar 

  133. Oguchi, Y., Kummer, E., Seyffer, F., Berynskyy, M., Anstett, B., Zahn, R., & Bukau, B. (2012). A tightly regulated molecular toggle controls AAA+ disaggregase. Nature Structural & Molecular Biology, 19(12), 1338–1346. https://doi.org/10.1038/nsmb.2441.

    Article  CAS  Google Scholar 

  134. Hayashi, S., Nakazaki, Y., Kagii, K., Imamura, H., & Watanabe, Y. (2017). Fusion protein analysis reveals the precise regulation between Hsp70 and Hsp100 during protein disaggregation. Scientific Reports, 7(1), 8648 https://doi.org/10.1038/s41598-017-08917-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Nan, L., Liu, Y., Ji, P., Feng, H., Chen, C., Wang, J., & Zhang, G. (2018). Trigger factor assisted self-assembly of canine parvovirus VP2 protein into virus-like particles in Escherichia coli with high immunogenicity. Virology Journal, 15(1), 103 https://doi.org/10.1186/s12985-018-1013-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Lu, X., He, S., Zong, H., Song, J., Chen, W., & Zhuge, B. (2016). Improved 1, 2, 4-butanetriol production from an engineered Escherichia coli by co-expression of different chaperone proteins. World Journal of Microbiology and Biotechnology, 32(9), 149 https://doi.org/10.1007/s11274-016-2085-5.

    Article  CAS  PubMed  Google Scholar 

  137. Mahamad, P., Boonchird, C., & Panbangred, W. (2016). High level accumulation of soluble diphtheria toxin mutant (CRM197) with co-expression of chaperones in recombinant Escherichia coli. Applied Microbiology and Biotechnology, 100(14), 6319–6330. https://doi.org/10.1007/s00253-016-7453-4.

    Article  CAS  PubMed  Google Scholar 

  138. Liu, C., Feng, H., Liu, Y., Chen, Y., Yang, S., Deng, R., & Zhang, G. (2020). Soluble FMDV VP1 proteins fused with calreticulin expressed in Escherichia coli under the assist of trigger factor16 (Tf16) formed into high immunogenic polymers. International Journal of Biological Macromolecules, 155, 1532–1540. https://doi.org/10.1016/j.ijbiomac.2019.11.130.

    Article  CAS  PubMed  Google Scholar 

  139. Piao, D.-C., Shin, D.-W., Kim, I.-S., Li, H.-S., Oh, S.-H., Singh, B., & Choi, Y.-J. (2016). Trigger factor assisted soluble expression of recombinant spike protein of porcine epidemic diarrhea virus in Escherichia coli. BMC Biotechnology, 16(1), 39 https://doi.org/10.1186/s12896-016-0268-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Oh, S., Kim Cho, Y.-S., Lee, H.-B., Lee, S.-M., Kim, W.-S., Hong, L., & Kang, S.-K. (2019). Enhancement of antigen-specific humoral immune responses and protein solubility through conjugation of bacterial flagellin, Vibrio vulnificus FlaB, to the N-terminus of porcine epidemic diarrhea virus surface protein antigen S0. Journal of Veterinary Science, 20(6), e70 https://doi.org/10.4142/jvs.2019.20.e70.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Avila, G. A., Ramirez, D. H., Hildenbrand, Z. L., Jacquez, P., Chiocca, S., Sun, J., & Xiao, C. (2015). Expression and in vitro functional analyses of recombinant Gam1 protein. Protein Expression and Purification, 105, 47–53.

    Article  CAS  PubMed  Google Scholar 

  142. Cao, T., Zhang, Z., Liu, Z.-G., Dou, X., Zhang, J., Zhang, W., & Yu, B. (2016). High-level expression and purification of the major house dust mite allergen Der p 2 in Escherichia coli. Protein Expression and Purification, 121, 97–102. https://doi.org/10.1016/j.pep.2016.01.012.

    Article  CAS  PubMed  Google Scholar 

  143. Miranda, B. N. M., Fotoran, W. L., Canduri, F., Souza, D. H. F., Wunderlich, G., & Carrilho, E. (2018). Heterologous expression of Homo sapiens alpha-folate receptors in E. coli by fusion with a trigger factor for enhanced solubilization. Protein Expression and Purification, 142, 75–80. https://doi.org/10.1016/j.pep.2017.10.006.

    Article  CAS  PubMed  Google Scholar 

  144. Guerrero, F., Ciragan, A., & Iwaï, H. (2015). Tandem SUMO fusion vectors for improving soluble protein expression and purification. Protein Expression and Purification, 116, 42–49. https://doi.org/10.1016/j.pep.2015.08.019.

    Article  CAS  PubMed  Google Scholar 

  145. Pan, D., Zha, X., Yu, X., & Wu, Y. (2016). Enhanced expression of soluble human papillomavirus L1 through coexpression of molecular chaperonin in Escherichia coli. Protein Expression and Purification, 120, 92–98. https://doi.org/10.1016/j.pep.2015.12.016.

    Article  CAS  PubMed  Google Scholar 

  146. Klermund, L., Riederer, A., Groher, A., & Castiglione, K. (2015). High-level soluble expression of a bacterial N-acyl-d-glucosamine 2-epimerase in recombinant Escherichia coli. Protein Expression and Purification, 111, 36–41. https://doi.org/10.1016/j.pep.2015.03.009.

    Article  CAS  PubMed  Google Scholar 

  147. Yu, T.-H., Yi, Y.-C., Shih, I.-T., & Ng, I.-S. (2020). Enhanced 5-Aminolevulinic acid production by Co-expression of codon-optimized hemA gene with Chaperone in genetic engineered Escherichia coli. Applied Biochemistry and Biotechnology, 191, 299–312. https://doi.org/10.1007/s12010-019-03178-9.

    Article  CAS  PubMed  Google Scholar 

  148. Wang, Z., Zhang, M., Lv, X., Fan, J., Zhang, J., Sun, J. & Shen, Y. (2018). GroEL/ES mediated the in vivo recovery of TRAIL inclusion bodies in Escherichia coli. Scientific reports, 8(1), 15766. https://doi.org/10.1038/s41598-018-34090-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Veisi, K., Farajnia, S., Zarghami, N., Khorshid, H. R. K., Samadi, N., Khosroshahi, S. A., & Jaliani, H. Z. (2015). Chaperone-assisted soluble expression of a humanized anti-EGFR ScFv antibody in E. Coli. Advanced Pharmaceutical Bulletin, 5, 621 Suppl 1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Schmalhausen, E. V., Shumkov, M. S., Muronetz, V. I., & Švedas, V. K. (2019). Expression of glyceraldehyde-3-phosphate dehydrogenase from M. tuberculosis in E. coli. Purification and characteristics of the untagged recombinant enzyme. Protein Expression and Purification, 157, 28–35. https://doi.org/10.1016/j.pep.2019.01.010.

    Article  CAS  PubMed  Google Scholar 

  151. Zou, W., Liu, X., Zhao, X., Wang, J., Chen, D., Li, J., … Hua, Z. (2015). Expression, purification, and characterization of recombinant human L-chain ferritin. Protein Expression and Purification, 119. https://doi.org/10.1016/j.pep.2015.11.018

  152. Zou, W., Liu, X., Chen, D., Wang, J., Zhao, X., Li, J., & Hua, Z. (2016). Expression, purification, and characterization of recombinant human H-chain ferritin. Preparative Biochemistry & Biotechnology, 46(8), 833–837. https://doi.org/10.1080/10826068.2016.1141300.

    Article  CAS  Google Scholar 

  153. Huang, M., Nan, Lu, X. Y., Zong, H., Zhuge, B., & Shen, W. (2018). Bioproduction of trans-10,cis-12-conjugated linoleic acid by a highly soluble and conveniently extracted linoleic acid isomerase and an extracellularly expressed lipase from recombinant Escherichia coli strains. Journal of Microbiology and Biotechnology, 28(5), 739–747. https://doi.org/10.4014/jmb.1802.02007.

    Article  CAS  PubMed  Google Scholar 

  154. Xu, G.-C., Li, L., Han, R.-Z., Dong, J.-J., & Ni, Y. (2016). Characterization and soluble expression of d-hydantoinase from pseudomonas fluorescens for the synthesis of d-amino acids. Applied Biochemistry and Biotechnology, 179(1), 1–15. https://doi.org/10.1007/s12010-015-1975-6.

    Article  CAS  PubMed  Google Scholar 

  155. Uthailak, N., Mahamad, P., Chittavanich, P., Yanarojana, S., Wijagkanalan, W., Petre, J., & Panbangred, W. (2017). Molecular cloning, structural modeling and the production of soluble triple-mutated diphtheria toxoid (K51E/G52E/E148K) co-expressed with molecular Chaperones in recombinant Escherichia coli. Molecular Biotechnology, 59(4–5), 117–127. https://doi.org/10.1007/s12033-017-0001-3.

    Article  CAS  PubMed  Google Scholar 

  156. Tong, Y., Feng, S., Xin, Y., Yang, H., Zhang, L., Wang, W., & Chen, W. (2016). Enhancement of soluble expression of codon-optimized Thermomicrobium roseum sarcosine oxidase in Escherichia coli via chaperone co-expression. Journal of Biotechnology, 218, 75–84. https://doi.org/10.1016/j.jbiotec.2015.11.018.

    Article  CAS  PubMed  Google Scholar 

  157. Vahdani, F., Ghafouri, H., Sarikhan, S., & Khodarahmi, R. (2019). Molecular cloning, expression, and functional characterization of 70-kDa heat shock protein, DnaK, from Bacillus halodurans. International journal of biological macromolecules, 137, 151–159.

    Article  CAS  PubMed  Google Scholar 

  158. Pei, X., Wang, Q., Meng, L., Li, J., Yang, Z., Yin, X., & Wu, J. (2015). Chaperones-assisted soluble expression and maturation of recombinant Co-type nitrile hydratase in Escherichia coli to avoid the need for a low induction temperature. Journal of Biotechnology, 203, 9–16.

    Article  CAS  PubMed  Google Scholar 

  159. Alfi, A., Zhu, B., Damnjanovic, J., Kojima, T., Iwasaki, Y., & Nakano, H. (2019). Production of active manganese peroxidase in Escherichia coli by co-expression of chaperones and in vitro maturation by ATP-dependent chaperone release. Journal of Bioscience and Bioengineering, 128(3), 290–295. https://doi.org/10.1016/j.jbiosc.2019.02.011.

    Article  CAS  PubMed  Google Scholar 

  160. Farajnia, S., Ghorbanzadeh, V., & Dariushnejad, H. (2020). Effect of molecular chaperone on the soluble expression of recombinant fab fragment in E. coli. International Journal of Peptide Research and Therapeutics, 26(1), 251–258.

    Article  CAS  Google Scholar 

  161. Malekian, R., Sima, S., Jahanian-Najafabadi, A., Moazen, F., & Akbari, V. (2019). Improvement of soluble expression of GM-CSF in the cytoplasm of Escherichia coli using chemical and molecular chaperones. Protein Expression and Purification, 160, 66–72.

    Article  CAS  PubMed  Google Scholar 

  162. Li, D., Fu, G., Tu, R., Jin, Z., & Zhang, D. (2019). High-efficiency expression and secretion of human FGF21 in Bacillus subtilis by intercalation of a mini-cistron cassette and combinatorial optimization of cell regulatory components. Microbial Cell Factories, 18(1), 17 https://doi.org/10.1186/s12934-019-1066-4.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Yousefi, M., Farajnia, S., Mokhtarzadeh, A., Akbari, B., Khosroshahi, S. A., Mamipour, M., & Ahmadzadeh, V. (2018). Soluble expression of humanized anti-CD20 single chain antibody in Escherichia coli by cytoplasmic chaperones co-expression. Avicenna Journal of Medical Biotechnology, 10(3), 141.

    PubMed  PubMed Central  Google Scholar 

  164. Dariushnejad, H., Farajnia, S., Zarghami, N., Aria, M., & Tanomand, A. (2019). Effect of DnaK/DnaJ/GrpE and DsbC Chaperons on periplasmic expression of fab antibody by E. coli SEC Pathway. International Journal of Peptide Research and Therapeutics, 25(1), 67–74. https://doi.org/10.1007/s10989-017-9637-x.

    Article  CAS  Google Scholar 

  165. de Marco, A., Deuerling, E., Mogk, A., Tomoyasu, T., & Bukau, B. (2007). Chaperone-based procedure to increase yields of soluble recombinant proteins produced in E. coli. BMC biotechnology, 7(1), 32.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Hansen, S. B., Laursen, N. S., Andersen, G. R., & Andersen, K. R. (2017). Introducing site-specific cysteines into nanobodies for mercury labelling allows de novo phasing of their crystal structures. Acta Crystallographica Section D: Structural Biology, 73(10), 804–813. https://doi.org/10.1107/S2059798317013171.

    Article  CAS  Google Scholar 

  167. Bertelsen, E. B., Chang, L., Gestwicki, J. E., & Zuiderweg, E. R. (2009). Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate. Proceedings of the National Academy of Sciences, 106(21), 8471–8476.

    Article  CAS  Google Scholar 

  168. Kityk, R., Kopp, J., Sinning, I., & Mayer, M. P. (2012). Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones. Molecular cell, 48(6), 863–874.

    Article  CAS  PubMed  Google Scholar 

  169. Carroni, M., Kummer, E., Oguchi, Y., Wendler, P., Clare, D. K., Sinning, I., & Saibil, H. R. (2014). Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation. eLife, 3, e02481 https://doi.org/10.7554/eLife.02481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Thomas, A. S., Mao, S., & Elcock, A. H. (2013). Flexibility of the bacterial chaperone trigger factor in microsecond-timescale molecular dynamics simulations. Biophysical Journal, 105(3), 732–744. https://doi.org/10.1016/j.bpj.2013.06.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Koike-Takeshita, A., Arakawa, T., Taguchi, H., & Shimamura, T. (2014). Crystal structure of a symmetric football-shaped GroEL:GroES2-ATP14 complex determined at 3.8Å reveals rearrangement between two GroEL rings. Journal of Molecular Biology, 426(21), 3634–3641. https://doi.org/10.1016/j.jmb.2014.08.017.

    Article  CAS  PubMed  Google Scholar 

  172. Wu, C.-C., Naveen, V., Chien, C.-H., Chang, Y.-W., & Hsiao, C.-D. (2012). Crystal structure of DnaK protein complexed with nucleotide exchange factor GrpE in DnaK chaperone system: insight into intermolecular communication. The Journal of Biological Chemistry, 287(25), 21461–21470. https://doi.org/10.1074/jbc.M112.344358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Li, J., & Sha, B. (2002). Crystal structure of E. coli Hsp100 ClpB nucleotide-binding domain 1 (NBD1) and mechanistic studies on ClpB ATPase activity. Journal of Molecular Biology, 318(4), 1127–1137. https://doi.org/10.1016/S0022-2836(02)00188-2.

    Article  CAS  PubMed  Google Scholar 

  174. Chi, H., Wang, X., Li, J., Ren, H., & Huang, F. (2016). Chaperonin-enhanced Escherichia coli cell-free expression of functional CXCR4. Journal of Biotechnology, 231, 193–200. https://doi.org/10.1016/j.jbiotec.2016.06.017.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Biochemistry, Kinnaird College for Women, Lahore, Punjab, Pakistan

    Komal Fatima, Fatima Naqvi & Hooria Younas

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  1. Komal Fatima
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  2. Fatima Naqvi
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  3. Hooria Younas
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Correspondence to Hooria Younas.

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Fatima, K., Naqvi, F. & Younas, H. A Review: Molecular Chaperone-mediated Folding, Unfolding and Disaggregation of Expressed Recombinant Proteins. Cell Biochem Biophys 79, 153–174 (2021). https://doi.org/10.1007/s12013-021-00970-5

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