Skip to main content
SpringerLink
Log in

Elucidation of Diverse Physico-Chemical Parameters in Mammalian Small Heat Shock Proteins: A Comprehensive Classification and Structural and Functional Exploration Using In Silico Approach

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Small heat shock proteins (sHSPs), often known as molecular chaperones, are most prevalent in nature. Under certain stress-induced conditions, these sHSPs act as an ATP-independent variation and thus prevent the inactivation of various non-native substrate proteins and their aggregation. They also assist other ATP-dependent chaperones in the refolding of these substrates. In the case of prokaryotes and lower eukaryotes, the chaperone functions of sHSPs can bind a wide range of cellular proteins but preferentially protect translation-related proteins and metabolic enzymes. Eukaryotes usually encode a larger number of sHSPs than those of prokaryotes. The chaperone functions of mammalian sHSPs are regulated by phosphorylation in cells and also by temperature. Their sHSPs have different sub-cellular compartments and cell/tissue specificity. The substrate proteins of mammalian sHSPs or eukaryotic sHSPs accordingly reflect their multi-cellular complexity. The sHSPs of animals play roles in different physiological processes as cell differentiation, apoptosis, and longevity. In this work, the characterization, location, tissue specificity, and functional diversity of sHSPs from seven different mammalian species with special emphasis on humans have been studied. Through this extensive work, a novel and significant attempt have been made to classify them based on their omnipresence, tissue specificity, localization, secondary structure, probable mutations, and evolutionary significance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig 4.

Similar content being viewed by others

Data Availability

The data are available upon request.

References

  1. Heirbaut, M., Beelen, S., Strelkov, S. V., & Weeks, S. D. (2014). Dissecting the functional role of the N-terminal domain of the human small heat shock protein HSPB6. PLoS One, 9(8), e105892. https://doi.org/10.1371/journal.pone.0105892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ferns, G., Shams, S., & Shafi, S. (2006). Heat shock protein 27: its potential role in vascular disease. International Journal of Experimental Pathology, 87(4), 253–274. https://doi.org/10.1111/j.1365-2613.2006.00484.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mogk, A., & Bukau, B. (2017). Role of sHSPs in organizing cytosolic protein aggregation and disaggregation. Cell Stress & Chaperones, 22(4), 493–502. https://doi.org/10.1007/s12192-017-0762-4.

    Article  CAS  Google Scholar 

  4. Sugiyama, Y., Suzuki, A., Kishikawa, M., Akutsu, R., Hirose, T., & Waye, M. M. (2000). Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation. The Journal of Biological Chemistry, 275(2), 1095–1104. https://doi.org/10.1074/jbc.275.2.1095.

    Article  CAS  PubMed  Google Scholar 

  5. Yoshida, K., Aki, T., Harada, K., Shama, K. M., Kamoda, Y., Suzuki, A., & Ohno, S. (1999). Translocation of HSP27 and MKBP in ischemic heart. Cell Structure and Function, 24(4), 181–185. https://doi.org/10.1247/csf.24.181.

    Article  CAS  PubMed  Google Scholar 

  6. Mymrikov, E., Seit-Nebi, A., & Gusev, N. (2011). Large potentials of small heat shock proteins. Physiological Reviews, 91(4), 1123–1159. https://doi.org/10.1152/physrev.00023.

    Article  CAS  PubMed  Google Scholar 

  7. Kriehuber, T., Rattei, T., Weinmaier, T., Bepperling, A., Haslbeck, M., & Buchner, J. (2010). Independent evolution of the core domain and its flanking sequences in small heat shock proteins. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 24(10), 3633–3642. https://doi.org/10.1096/fj.10-156992.

    Article  CAS  Google Scholar 

  8. Taylor, R. P., & Benjamin, I. J. (2005). Small heat shock proteins: a new classification scheme in mammals. Journal of Molecular and Cellular Cardiology, 38(3), 433–444. https://doi.org/10.1016/j.yjmcc.2004.12.014.

    Article  CAS  PubMed  Google Scholar 

  9. Benjamin, I. J., & McMillan, D. R. (1998). Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circulation Research, 83(2), 117–132. https://doi.org/10.1161/01.res.83.2.117.

    Article  CAS  PubMed  Google Scholar 

  10. Lam, W. Y., Wing, S. K., Tsui, P. T., Law, Luk, S. C., Fung, K. P., & Lee, C. Y. (1996). Isolation and characterization of a human heart cDNA encoding a new member of the small heat shock protein family—HSPL27. Biochimica et Biophysica Acta, 1314(1-2), 120–124. https://doi.org/10.1016/s0167-4889(96)00121-8.

    Article  CAS  PubMed  Google Scholar 

  11. The UniProt Consortium. (2019). UniProt: the universal protein knowledgebase. Nucleic Acids Research, 47(D1), D506–D515. https://doi.org/10.1093/nar/gky1049.

    Article  CAS  Google Scholar 

  12. Itaya, H., Oshita, K., Arakawa, K., & Tomita, M. (2013). GEMBASSY: an EMBOSS associated software package for comprehensive genome analyses. Source Code for Biology and Medicine, 8(1), 17. https://doi.org/10.1186/1751-0473-8-17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Simossis, V. A., & Heringa, J. (2005). PRALINE: a multiple sequence alignment toolbox that integrates homology-extended and secondary structure information. Nucleic Acids Research, 33(Web Server issue), W289–W294. https://doi.org/10.1093/nar/gki390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Thompson, J. D., Higgins, D. G., & Gibson, T. J. (1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research, 22(22), 4673–4680. https://doi.org/10.1093/nar/22.22.4673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. El-Gebali, S., Mistry, J., Bateman, A., Eddy, R. S., Luciani, A., Potter, C. S., Qureshi, M., Richardson, J. L., Salazar, A. G., Smart, A., Sonnhammer, L. L. E., Hirsh, L., Paladin, L., Piovesan, D., Tosatto, E. C. S., & Finn, D. R. (2019). The Pfam protein families database in 2019.Nucleic. Acids Research, 47(D1), D427–D432. https://doi.org/10.1093/nar/gky995.

    Article  CAS  Google Scholar 

  16. Narberhaus, F. (2002). Alpha-crystallin-type heat shock proteins: socializing minichaperones in the context of a multichaperone network. Microbiology and Molecular Biology Reviews: MMBR, 66(1), 64–93. https://doi.org/10.1128/mmbr.66.1.64-93.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kouza, M., Faraggi, E., Kolinski, A., & Kloczkowski, A. (2017). The GOR method of protein secondary structure prediction and its application as a protein aggregation prediction tool. Methods in Molecular Biology (Clifton, N.J.), 1484, 7–24. https://doi.org/10.1007/978-1-4939-6406-2_2.

    Article  CAS  Google Scholar 

  18. Dereeper, A., Guignon, V., Blanc, G., Audic, S., Buffet, S., Chevenet, F., Dufayard, J. F., Guindon, S., Lefort, V., Lescot, M., Claverie, J. M., & Gascuel, O. (2008). Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Research, 36(Web Server issue), W465–W469. https://doi.org/10.1093/nar/gkn180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Islamovic, E., Duncan, A., Bers, D. M., Gerthoffer, W. T., & Mestril, R. (2007). Importance of small heat shock protein 20 (hsp20) C-terminal extension in cardioprotection. Journal of Molecular and Cellular Cardiology, 42(4), 862–869. https://doi.org/10.1016/j.yjmcc.2007.01.002.

    Article  CAS  PubMed  Google Scholar 

  20. Boelens, W. C., Van Boekel, M. A., & De Jong, W. W. (1998). HspB3, the most deviating of the six known human small heat shock protein. Biochimica et Biophysica Acta, 1388(2), 513–516. https://doi.org/10.1016/s0167-4838(98)00215-5.

    Article  CAS  PubMed  Google Scholar 

  21. Sha, L., Hou, N., Zhang, M., Ma, Q., & Shi, C. (2019). High α B-crystallin and p53 co-expression is associated with poor prognosis in ovarian cancer. Bioscience Reports, 39(6), BSR20182407. https://doi.org/10.1042/BSR20182407.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Iwaki, A., Nagano, T., Nakagawa, M., Iwaki, T., & Fukumaki, Y. (1997). Identification and characterization of the gene encoding a new member of the alpha-crystallin/small HSP family, closely linked to the alpha-B crystallin gene in a head-to-head manner. Genomics, 45(2), 386–394. https://doi.org/10.1006/geno.1997.4956.

    Article  CAS  PubMed  Google Scholar 

  23. Arrigo, A. P., Simon, S., Gibert, B., Kretz-Remy, C., Nivon, M., Czekalla, A., Guillet, D., Moulin, M., Diaz-Latoud, C., & Vicart, P. (2007). Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Letters, 581(19), 3665–3674. https://doi.org/10.1016/j.febslet.2007.04.033.

    Article  CAS  PubMed  Google Scholar 

  24. Suzuki, A., Sugiyama, Y., Hayashi, Y., Nyu-i, N., Yoshida, M., & Nonaka, I. (1998). A novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase. The Journal of Cell Biology, 140(5), 1113–1124. https://doi.org/10.1083/jcb.140.5.1113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. McGuffin, L., Bryson, K., & Jones, D. (2000). The PSIPRED protein structure prediction server. Bioinformatics (Oxford, England), 16(4), 404–405. https://doi.org/10.1093/bioinformatics/16.4.404.

    Article  CAS  Google Scholar 

  26. Gastmann, O., Burfeind, P., Gunther, E., Hameister, H., Szpirer, C., & Hoyer-Fender, S. (1993). Sequence, expression, and chromosomal assignment of a human sperm outer dense fiber gene. Molecular Reproduction and Development, 36(4), 407–418. https://doi.org/10.1002/mrd.1080360402.

    Article  CAS  PubMed  Google Scholar 

  27. Waters, E. R., & Rioflorido, I. (2007). Evolutionary analysis of the small heat shock proteins in five complete algal genomes. Journal of Molecular Evolution, 65(2), 162–174. https://doi.org/10.1007/s00239-006-0223-7.

    Article  CAS  PubMed  Google Scholar 

  28. Fan, G. C., Chu, G., Mitton, B., Song, Q., Yuan, Q., & Kranias, E. G. (2004). Small heat-shock protein Hsp20 phosphorylation inhibits β-agonist-induced cardiac apoptosis. Circulation Research, 94(11), 1474–1482. https://doi.org/10.1161/01.res.0000129179.66631.00.

    Article  CAS  PubMed  Google Scholar 

  29. Basha, E., Jones, C., Wysocki, V., & Vierling, E. (2010). Mechanistic differences between two conserved classes of small heat shock proteins found in the plant cytosol. The Journal of Biological Chemistry, 285(15), 11489–11497. https://doi.org/10.1074/jbc.M109.074088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Siddique, M., Gernhard, S., Koskull-Doring, P., Vierling, E., & Scharf, K. D. (2008). The plant sHSP superfamily: five new members in Arabidopsis thaliana with unexpected properties. Cell Stress & Chaperones, 13(2), 183–197. https://doi.org/10.1007/s12192-008-0032-6.

    Article  CAS  Google Scholar 

  31. van Heijst, J. W., Niessen, H. W., Musters, R. J., van Hinsbergh, V. W., Hoekman, K., & Schalkwijk, C. G. (2006). Argpyrimidine-modified heat shock protein 27 in human non-small cell lung cancer: a possible mechanism for evasion of apoptosis. Cancer Letters, 241(2), 309–319. https://doi.org/10.1016/j.canlet.2005.10.042.

    Article  CAS  PubMed  Google Scholar 

  32. Nicolaou, P., Knöll, R., Haghighi, K., Guo-Chang, F., Dorn, G. W., Hasenfu, G., & Kranias, E. G. (2008). Human mutation in the anti-apoptotic heat shock protein 20 abrogates its cardioprotective effects. The Journal of Biological Chemistry, 283(48), 33465–33471. https://doi.org/10.1074/jbc.M802307200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sigrist, C. J., Cerutti, L., Hulo, N., Gattiker, A., Falquet, L., Pagni, M., Bairoch, A., & Bucher, P. (2002). PROSITE: a documented database using patterns and profiles as motif descriptors. Briefings in Bioinformatics, 3(3), 265–274. https://doi.org/10.1093/bib/3.3.265.

    Article  CAS  PubMed  Google Scholar 

  34. Chu, G., Egnaczyk, G. F., Zhao, W., Jo, S. H., Fan, G. C., Maggio, J. E., Xiao, R. P., & Kranias, E. G. (2004). Phosphoproteome analysis of cardiomyocytes subjected to beta-adrenergic stimulation: identification and characterization of a cardiac heat shock protein p20. Circulation Research, 94(2), 184–193. https://doi.org/10.1161/01.RES.0000107198.90218.21.

    Article  CAS  PubMed  Google Scholar 

  35. Pandey, B., Kaur, A., Gupta, O. P., Sharma, I., & Sharma, P. (2000). Identification of HSP20 gene family in wheat and barley and their differential expression profiling under heat stress. Applied Biochemistry and Biotechnology, 175(5), 2427–2446. https://doi.org/10.1007/s12010-014-1420-2.

    Article  CAS  Google Scholar 

  36. Zhu, Y. H., Ma, T. M., & Wang, X. (2005). Gene transfer of heat-shock protein 20 protects against ischemia/reperfusion injury in rat hearts. Acta Pharmacologica Sinica, 26(10), 1193–1200. https://doi.org/10.1111/j.1745-7254.2005.00139.x.

    Article  CAS  PubMed  Google Scholar 

  37. Kappé, G., Franck, E., Verschuure, P., Boelens, W. C., Leunissen, J. A., & de Jong, W. W. (2003). The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress & Chaperones, 8(1), 53–61. https://doi.org/10.1379/1466-1268(2003)8<53:thgecs>2.0.co;2.

    Article  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the help from the DBT-funded BIF (Bioinformatics facility center), University of Kalyani, West Bengal are also acknowledged for furnishing all the necessary infrastructural facilities to pursue the whole study.

Funding

The research work is supported by the Department of Science and Technology and Biotechnology of West Bengal Govt. who rendered required financial support to carry on with the research works through R&D project SA. No./ST/P/S&T/1-G14/2018. Financial support was also provided by UGC-SAP-DSR-II and DST-PURSE-2.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia, West Bengal, 741235, India

    Sangeeta Mitra, Angshuman Bagchi & Rakhi Dasgupta

Authors
  1. Sangeeta Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angshuman Bagchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rakhi Dasgupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AB and RDG devised the project. SM performed the experimentations. All the authors wrote the manuscript and agreed to submit the manuscript.

Corresponding authors

Correspondence to Angshuman Bagchi or Rakhi Dasgupta.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

Not applicable

Consent to Participate

Not applicable

Consent to Publish

All authors agreed to submit the manuscript.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mitra, S., Bagchi, A. & Dasgupta, R. Elucidation of Diverse Physico-Chemical Parameters in Mammalian Small Heat Shock Proteins: A Comprehensive Classification and Structural and Functional Exploration Using In Silico Approach. Appl Biochem Biotechnol 193, 1836–1852 (2021). https://doi.org/10.1007/s12010-021-03497-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-021-03497-w

Keywords

Search

Navigation