Advertisement

Biophysical Reviews

, Volume 8, Issue 2, pp 107–120 | Cite as

A review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering

  • Júlio C. BorgesEmail author
  • Thiago V. Seraphim
  • Paulo R. Dores-Silva
  • Leandro R. S. BarbosaEmail author
Review

Abstract

Intrinsic flexibility is closely related to protein function, and a plethora of important regulatory proteins have been found to be flexible, multi-domain or even intrinsically disordered. On the one hand, understanding such systems depends on how these proteins behave in solution. On the other, small-angle X-ray scattering (SAXS) is a technique that fulfills the requirements to study protein structure and dynamics relatively quickly with few experimental limitations. Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins containing flexible and/or disordered regions that play central roles in cellular proteostasis. Here, we review the structure and function of these proteins by SAXS. Our general approach includes the use of SAXS data to determine size and shape parameters, as well as protein shape reconstruction and their validation by using accessory biophysical tools. Some remarkable examples are presented that exemplify the potential of the SAXS technique. Protein structure can be determined in solution even at limiting protein concentrations (for example, human mortalin, a mitochondrial Hsp70 chaperone). The protein organization, flexibility and function (for example, the J-protein co-chaperones), oligomeric status, domain organization, and flexibility (for the Hsp90 chaperone and the Hip and Hep1 co-chaperones) may also be determined. Lastly, the shape, structural conservation, and protein dynamics (for the Hsp90 chaperone and both p23 and Aha1 co-chaperones) may be studied by SAXS. We believe this review will enhance the application of the SAXS technique to the study of the molecular chaperones.

Keywords

SAXS Multi-domain proteins Protein dynamics Molecular chaperones Mortalin Hsp70 

Notes

Acknowledgments

J.C. Borges thanks FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) and CNPq (Conselho Nacional de Pesquisa e Desenvolvimento) for financial support (grants #2007/05001-4, #2011/23110-0, #2012/50161-8, #2014/07206-6 and #471415/2013-8) and a Research Fellowship (#306125/2012-9). L.R.S. Barbosa also thanks FAPESP and CNPq for financial support (#2012/50161-8, #2015/07572-5, #2015/15822-1 and #303048/2012-3). P.R. Dores-Silva thanks FAPESP for grant (#2014/16646-0). We also thank the Brazilian Synchrotron Light Laboratory (LNLS/CNPEM-ABTLuS, Campinas, Brazil) for the use of the SAXS beamline.

Compliance with Ethical Standards

Conflict of interest

Júlio C. Borges declares that he has no conflict of interest.

Thiago V. Seraphim declares that he has no conflict of interest.

Paulo R. Dores-Silva declares that he has no conflict of interest.

Leandro R. S. Barbosa declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C, Pearl LH (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440:1013–1017PubMedCrossRefGoogle Scholar
  2. Arndt V, Rogon C, Hohfeld J (2007) To be, or not to be—molecular chaperones in protein degradation. Cell Mol Life Sci 64:2525–2541PubMedCrossRefGoogle Scholar
  3. Avila CL, Torres-Bugeau CM, Barbosa LR, Sales EM, Ouidja MO, Socías SB, Celej MS, Raisman-Vozari R, Papy-Garcia D, Itri R, Chehín RN (2014) Structural characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase protofibrils preventing alpha-synuclein oligomeric species toxicity. J Biol Chem 289:13838–13850PubMedPubMedCentralCrossRefGoogle Scholar
  4. Barbosa LRS, Spinozzi F, Mariani P, Itri R (2013) Small-angle X-ray scattering applied to proteins in solution. In: Ruso JM, Piñeiro Á (eds) Proteins in solution and at interfaces: methods and applications in biotechnology and materials science. Wiley, New York, pp 49–72Google Scholar
  5. Batista FA, Gava LM, Pinheiro GM, Ramos CH, Borges JC (2015a) From conformation to interaction: techniques to explore the Hsp70/ Hsp90 network. Curr Protein Pept Sci 16:735–753PubMedCrossRefGoogle Scholar
  6. Batista FAH, Almeida GS, Seraphim TV, Silva KP, Murta SMF, Barbosa LRS, Borges JC (2015b) Identification of two p23 co-chaperone isoforms in Leishmania braziliensis exhibiting similar structures and Hsp90 interaction properties despite divergent stabilities. FEBS J 282:388–406PubMedCrossRefGoogle Scholar
  7. Berlow RB, Dyson HJ, Wright PE (2015) Functional advantages of dynamic protein disorder. FEBS Lett 589:2433–2440PubMedCrossRefGoogle Scholar
  8. Bernado P, Mylonas E, Petoukhov MV, Blackledge M, Svergun DI (2007) Structural characterization of flexible proteins using small-angle x-ray scattering. J Am Chem Soc 129:5656–5664PubMedCrossRefGoogle Scholar
  9. Blanchet CE, Svergun DI (2013) Small-angle x-ray scattering on biological macromolecules and nanocomposites. Annu Rev Phys Chem 64:37–54PubMedCrossRefGoogle Scholar
  10. Bohnert M, Pfanner N, van der Laan M (2007) A dynamic machinery for import of mitochondrial precursor proteins. FEBS Lett 581:2802–2810PubMedCrossRefGoogle Scholar
  11. Borges JC, Ramos CHI (2005) Protein folding assisted by chaperones. Protein Pept Lett 12:257–261PubMedCrossRefGoogle Scholar
  12. Borges JC, Fischer H, Craievich AF, Ramos CH (2005) Low resolution structural study of two human HSP40 chaperones in solution. DJA1 from subfamily A and DJB4 from subfamily B have different quaternary structures. J Biol Chem 280:13671–13681PubMedCrossRefGoogle Scholar
  13. Borges JC, Seraphim TV, Mokry DZ, Almeida FCL, Cyr DM, Ramos CHI (2012) Identification of regions involved in substrate binding and dimer stabilization within the central domains of yeast Hsp40 Sis1. PLoS ONE 7:e50927PubMedPubMedCentralCrossRefGoogle Scholar
  14. Botha M, Pesce ER, Blatch GL (2007) The Hsp40 proteins of Plasmodium falciparum and other apicomplexa: regulating chaperone power in the parasite and the host. Int J Biochem Cell Biol 39:1781–1803PubMedCrossRefGoogle Scholar
  15. Bron P, Giudice E, Rolland JP, Buey RM, Barbier P, Díaz JF, Peyrot V, Thomas D, Garnier C (2008) Apo-Hsp90 coexists in two open conformational states in solution. Biol Cell 100:413–425PubMedCrossRefGoogle Scholar
  16. Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125:443–451PubMedCrossRefGoogle Scholar
  17. Burri L, Vascotto K, Fredersdorf S, Tiedt R, Hall MN, Lithgow T (2004) Zim17, a novel zinc finger protein essential for protein import into mitochondria. J Biol Chem 279:50243–50249PubMedCrossRefGoogle Scholar
  18. Chadli A, Bouhouche I, Sullivan W, Stensgard B, McMahon N, Catelli MG, Toft DO (2000) Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90. Proc Natl Acad Sci U S A 97:12524–12529PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cunningham CN, Southworth DR, Krukenberg KA, Agard DA (2012) The conserved arginine 380 of Hsp90 is not a catalytic residue, but stabilizes the closed conformation required for ATP hydrolysis. Protein Sci 21:1162–1171PubMedPubMedCentralCrossRefGoogle Scholar
  20. Cyr DM (1995) Cooperation of the molecular chaperone Ydj1 with specific Hsp70 homologs to suppress protein aggregation. FEBS Lett 359:129–132PubMedCrossRefGoogle Scholar
  21. Cyr DM, Ramos CH (2015) Specification of Hsp70 function by type I and type II Hsp40. In: The networking of chaperones by co-chaperones. Subcellular Biochemistry. Springer, Switzerland, pp 91–102Google Scholar
  22. da Silva KP, Borges JC (2011) The molecular chaperone Hsp70 family members function by a bidirectional heterotrophic allosteric mechanism. Protein Pept Lett 18:132–142PubMedCrossRefGoogle Scholar
  23. Daugaard M, Rohde M, Jaattela M (2007) The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 581:3702–3710PubMedCrossRefGoogle Scholar
  24. de la Torre JG, Huertas ML, Carrasco B (2000) Calculation of hydrodynamic properties of globular proteins from their atomic-level structure. Biophys J 78:719–730CrossRefGoogle Scholar
  25. Dittmar KD, Demady DR, Stancato LF, Krishna P, Pratt WB (1997) Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based chaperone machinery. J Biol Chem 272:21213–21220PubMedCrossRefGoogle Scholar
  26. Dolezal P, Likic V, Tachezy J, Lithgow T (2006) Evolution of the molecular machines for protein import into mitochondria. Science 313:314–318PubMedCrossRefGoogle Scholar
  27. Dores-Silva PR, Silva ER, Gomes FER, Silva KP, Barbosa LRS, Borges JC (2012) Low resolution structural characterization of the Hsp70-interacting protein—hip - from Leishmania braziliensis emphasizes its high asymmetry. Arch Biochem Biophys 520:88–98PubMedCrossRefGoogle Scholar
  28. Dores-Silva PR, Minari K, Ramos CHI, Barbosa LRS, Borges JC (2013) Structural and stability studies of the human mtHsp70-escort protein 1: an essential mortalin co-chaperone. Int J Biol Macromol 56:140–148PubMedCrossRefGoogle Scholar
  29. Dores-Silva PR, Barbosa LRS, Ramos CHI, Borges JC (2015a) Human mitochondrial Hsp70 (mortalin): shedding light on ATPase activity, interaction with adenosine nucleotides, solution structure and domain organization. PLoS ONE 10:e0117170PubMedPubMedCentralCrossRefGoogle Scholar
  30. Dores-Silva PR, Beloti LL, Minari K, Silva SMO, Barbosa LRS, Borges JC (2015b) Structural and functional studies of Hsp70-escort protein—Hep1 - of Leishmania braziliensis. Int J Biol Macromol 79:903–912PubMedCrossRefGoogle Scholar
  31. Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradovic Z (2002) Intrinsic disorder and protein function. Biochemistry 41:6573–6582PubMedCrossRefGoogle Scholar
  32. Dunker AK, Silman I, Uversky VN, Sussman JL (2008) Function and structure of inherently disordered proteins. Curr Opin Struct Biol 18:756–764PubMedCrossRefGoogle Scholar
  33. Echtenkamp FJ, Freeman BC (2014) Emergence and characterization of the p23 molecular chaperone. In: The molecular chaperones interaction networks in protein folding and degradation, vol 1, Interactomics and systems biology. Springer, New York, pp 207–232Google Scholar
  34. Echtenkamp FJ, Zelin E, Oxelmark E, Woo JI, Andrews BJ, Garabedian M, Freeman BC (2011) Global functional map of the p23 molecular chaperone reveals an extensive cellular network. Mol Cell 43:229–241PubMedPubMedCentralCrossRefGoogle Scholar
  35. Eckl JM, Richter K (2013) Functions of the Hsp90 chaperone system: lifting client proteins to new heights. Int J Biochem Mol Biol 4:157–165PubMedPubMedCentralGoogle Scholar
  36. Fan ACY, Young JC (2011) Function of cytosolic chaperones in Tom70-mediated mitochondrial import. Prot Pept Lett 18:122–131CrossRefGoogle Scholar
  37. Fan CY, Lee S, Cyr DM (2003) Mechanisms for regulation of Hsp70 function by Hsp40. Cell Stress Chaperones 8:309–316PubMedPubMedCentralCrossRefGoogle Scholar
  38. Fan CY, Lee S, Ren HY, Cyr DM (2004) Exchangeable chaperone modules contribute to specification of type I and type II Hsp40 cellular function. Mol Biol Cell 15:761–773PubMedPubMedCentralCrossRefGoogle Scholar
  39. Flynn JM, Mishra P, Bolon DN (2015) Mechanistic asymmetry in Hsp90 dimers. J Mol Biol 427:2904–2911PubMedCrossRefGoogle Scholar
  40. Forafonov F, Toogun OA, Grad I, Suslova E, Freeman BC, Picard D (2008) p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity. Mol Cell Biol 28:3446–3456PubMedPubMedCentralCrossRefGoogle Scholar
  41. Franke D, Svergun DI (2009) DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering. J Appl Cryst 42:342–346CrossRefGoogle Scholar
  42. Fukuchi S, Hosoda K, Homma K, Gojobori T, Nishikawa K (2011) Binary classification of protein molecules into intrinsically disordered and ordered segments. BMC Struct Biol 11:29PubMedPubMedCentralCrossRefGoogle Scholar
  43. Glatter O (1977) A new method for the evaluation of small-angle scattering data. J Appl Cryst 10:415–421CrossRefGoogle Scholar
  44. Glatter O, Kratky O (1982) Small angle x-ray scattering. Academic, New YorkGoogle Scholar
  45. Greene MK, Maskos K, Landry SJ (1998) Role of the J-domain in the cooperation of Hsp40 with Hsp70. Proc Natl Acad Sci U S A 95:6108–6113PubMedPubMedCentralCrossRefGoogle Scholar
  46. Guinier A (1939) X-ray diffraction at very low angles: applications to study of ultra-microscopic phenomena. Ann Phys 12:161–236Google Scholar
  47. Guinier A, Fournet G (1955) Small angle scattering of X-rays. Wiley, New YorkGoogle Scholar
  48. Harst A, Lin H, Obermann WM (2005) Aha1 competes with Hop, p50 and p23 for binding to the molecular chaperone Hsp90 and contributes to kinase and hormone receptor activation. Biochem J 387:789–796PubMedPubMedCentralCrossRefGoogle Scholar
  49. Hartl FU, Hayer-Hartl M (2002) Protein folding—molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858PubMedCrossRefGoogle Scholar
  50. Hohfeld J, Minami Y, Hartl FU (1995) Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell 83:589–598PubMedCrossRefGoogle Scholar
  51. Hu JB, Wu YK, Li JZ, Qian XG, Fu ZQ, Sha BD (2008) The crystal structure of the putative peptide-binding fragment from the human Hsp40 protein Hdj1. BMC Struct Biol 8:3PubMedPubMedCentralCrossRefGoogle Scholar
  52. Hura GL et al (2009) Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS). Nat Methods 6:606–612PubMedPubMedCentralCrossRefGoogle Scholar
  53. Jacques DA, Trewhella J (2010) Small-angle scattering for structural biology-expanding the frontier while avoiding the pitfalls. Protein Sci 19:642–657PubMedPubMedCentralCrossRefGoogle Scholar
  54. Johnson JL, Craig EA (2001) An essential role for the substrate-binding region of Hsp40s in Saccharomyces cerevisiae. J Cell Biol 152:851–856PubMedPubMedCentralCrossRefGoogle Scholar
  55. Kampinga HH, Craig EA (2010) The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Bio 11:579–592CrossRefGoogle Scholar
  56. Karagöz GE, Duarte AM, Ippel H, Uetrecht C, Sinnige T, van Rosmalen M, Hausmann J, Heck AJ, Boelens R, Rüdiger SG (2011) N-terminal domain of human Hsp90 triggers binding to the cochaperone p23. Proc Natl Acad Sci U S A 108:580–585PubMedPubMedCentralCrossRefGoogle Scholar
  57. Karzai AW, McMacken R (1996) A bipartite signaling mechanism involved in DnaJ-mediated activation of the Escherichia coli DnaK protein. J Biol Chem 271:11236–11246PubMedCrossRefGoogle Scholar
  58. Kaul SC, Deocaris CC, Wadhwa R (2007) Three faces of mortalin: a housekeeper, guardian and killer. Exp Gerontol 42:263–274PubMedCrossRefGoogle Scholar
  59. Kikhney AG, Svergun DI (2015) A practical guide to small angle X-ray scattering (SAXS) of flexible and intrinsically disordered proteins. FEBS Lett 589:2570–2577PubMedCrossRefGoogle Scholar
  60. Koch MHJ, Vachette P, Svergun DI (2003) Small-angle scattering: a view on the properties, structures and structural changes of biological macromolecules in solution. Q Rev Biophys 36:147–227PubMedCrossRefGoogle Scholar
  61. Koulov AV, LaPointe P, Lu B, Razvi A, Coppinger J, Dong MQ, Matteson J, Laister R, Arrowsmith C, Yates JR, Balch WE (2010) Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis. Mol Biol Cell 21:871–884PubMedPubMedCentralCrossRefGoogle Scholar
  62. Kratky O, Porod G (1949) Roentgenuntersuchung Geloester Fadenmolekuele. Rec Trav Chim Pays-Bas 68:1106–1122CrossRefGoogle Scholar
  63. Krukenberg KA, Forster F, Rice LM, Sali A, Agard DA (2008) Multiple conformations of E. coli Hsp90 in solution: insights into the conformational dynamics of Hsp90. Structure 16:755–765PubMedPubMedCentralCrossRefGoogle Scholar
  64. Krukenberg KA, Southworth DR, Street TO, Agard DA (2009a) pH-dependent conformational changes in bacterial Hsp90 reveal a Grp94-like conformation at pH 6 that is highly active in suppression of citrate synthase aggregation. J Mol Biol 390:278–291PubMedPubMedCentralCrossRefGoogle Scholar
  65. Krukenberg KA, Bottcher UM, Southworth DR, Agard DA (2009b) Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide. Protein Sci 18:1815–1827PubMedPubMedCentralCrossRefGoogle Scholar
  66. Krukenberg KA, Street TO, Lavery LA, Agard DA (2011) Conformational dynamics of the molecular chaperone Hsp90. Q Rev Biophys 44:229–255PubMedCrossRefGoogle Scholar
  67. Lamb JR, Tugendreich S, Hieter P (1995) Tetratrico peptide repeat interactions—to Tpr or not to Tpr. Trends Biochem Sci 20:257–259PubMedCrossRefGoogle Scholar
  68. Laufen T, Mayer MP, Beisel C, Klostermeier D, Mogk A, Reinstein J, Bukau B (1999) Mechanism of regulation of Hsp70 chaperones by DnaJ cochaperones. Proc Natl Acad Sci U S A 96:5452–5457PubMedPubMedCentralCrossRefGoogle Scholar
  69. Lemak A, Wu B, Yee A, Houliston S, Lee HW, Gutmanas A, Fang X, Garcia M, Semesi A, Wang YX, Prestegard JH, Arrowsmith CH (2014) Structural characterization of a flexible two-domain protein in solution using small angle X-ray scattering and NMR data. Structure 22:1862–1874PubMedCrossRefGoogle Scholar
  70. Li J, Buchner J (2013) Structure, function and regulation of the Hsp90 machinery. Biomed J 36:106–117PubMedCrossRefGoogle Scholar
  71. Li JZ, Oian XG, Sha B (2003) The crystal structure of the yeast Hsp40 Ydj1 complexed with its peptide substrate. Structure 11:1475–1483PubMedCrossRefGoogle Scholar
  72. Lotz GP, Lin H, Harst A, Obermann WM (2003) Aha1 binds to the middle domain of Hsp90, contributes to client protein activation, and stimulates the ATPase activity of the molecular chaperone. J Biol Chem 278:17228–17235PubMedCrossRefGoogle Scholar
  73. Lu Z, Cyr DM (1998) Protein folding activity of Hsp70 is modified differentially by the Hsp40 co-chaperones Sis1 and Ydj1. J Biol Chem 273:27824–27830PubMedCrossRefGoogle Scholar
  74. Ma B, Tsai CJ, Haliloglu T, Nussinov R (2011) Dynamic allostery: linkers are not merely flexible. Structure 19:907–917PubMedCrossRefGoogle Scholar
  75. Martinez-Yamout MA, Venkitakrishnan RP, Preece NE, Kroon G, Wright PE, Dyson HJ (2006) Localization of sites of interaction between p23 and Hsp90 in solution. J Biol Chem 281:14457–14464PubMedCrossRefGoogle Scholar
  76. Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684PubMedPubMedCentralCrossRefGoogle Scholar
  77. Mayer MP, Le Breton L (2015) Hsp90: breaking the symmetry. Mol Cell 58:8–20PubMedCrossRefGoogle Scholar
  78. McLaughlin SH, Sobott F, Yao ZP, Zhang W, Nielsen PR, Grossmann JG, Laue ED, Robinson CV, Jackson SE (2006) The co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins. J Mol Biol 356:746–758PubMedCrossRefGoogle Scholar
  79. Meimaridou E, Gooljar SB, Chapple JP (2009) From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J Mol Endocrinol 42:1–9PubMedCrossRefGoogle Scholar
  80. Mertens HDT, Svergun DI (2010) Structural characterization of proteins and complexes using small-angle X-ray solution scattering. J Struct Biol 172:128–141PubMedCrossRefGoogle Scholar
  81. Meyer P, Prodromou C, Hu B, Vaughan C, Roe SM, Panaretou B, Piper PW, Pearl LH (2003) Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol Cell 11:647–658PubMedCrossRefGoogle Scholar
  82. Meyer P, Prodromou C, Liao C, Hu B, Roe SM, Vaughan CK, Vlasic I, Panaretou B, Piper PW, Pearl LH (2004) Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. EMBO J 23:1402–1410PubMedCrossRefGoogle Scholar
  83. Mickler M, Hessling M, Ratzke C, Buchner J, Hugel T (2009) The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis. Nat Struct Mol Biol 16:281–286PubMedCrossRefGoogle Scholar
  84. Mokranjac D, Neupert W (2009) Thirty years of protein translocation into mitochondria: unexpectedly complex and still puzzling. Biochim Biophys Acta 1793:33–41PubMedCrossRefGoogle Scholar
  85. Mollerup J, Berchtold MW (2005) The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis. FEBS Lett 579:4187–4192PubMedCrossRefGoogle Scholar
  86. Momose T, Ohshima C, Maeda M, Endo T (2007) Structural basis of functional cooperation of Tim15/Zim17 with yeast mitochondrial Hsp70. EMBO Rep 8:664–670PubMedPubMedCentralCrossRefGoogle Scholar
  87. Nemoto T, Ohara-Nemoto Y, Ota M, Takagi T, Yokoyama K (1995) Mechanism of dimer formation of the 90-kDa heat-shock protein. Eur J Biochem 233:1–8PubMedCrossRefGoogle Scholar
  88. Nillegoda NB, Kirstein J, Szlachcic A, Berynskyy M, Stank A, Stengel F, Arnsburg K, Gao X, Scior A, Aebersold R, Guilbride DL, Wade RC, Morimoto RI, Mayer MP, Bukau B (2015) Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation. Nature 524:247–251PubMedPubMedCentralCrossRefGoogle Scholar
  89. Obermann WM, Sondermann H, Russo AA, Pavletich NP, Hartl FU (1998) In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol 143:901–910PubMedPubMedCentralCrossRefGoogle Scholar
  90. Olesen SH, Ingles DJ, Zhu JY, Martin MP, Betzi S, Georg GI, Tash JS, Schönbrunn E (2015) Stability of the human Hsp90-p50Cdc37 chaperone complex against nucleotides and Hsp90 inhibitors, and the influence of phosphorylation by casein kinase 2. Molecules 20:1643–1660PubMedPubMedCentralCrossRefGoogle Scholar
  91. Onuoha SC, Couistock ET, Grossmann JG, Jackson SE (2008) Structural studies on the co-chaperone Hop and its complexes with Hsp90. J Mol Biol 379:732–744PubMedCrossRefGoogle Scholar
  92. Ortore MG, Spinozzi F, Mariani P, Paciaroni A, Barbosa LR, Amenitsch H, Steinhart M, Ollivier J, Russo D (2009) Combining structure and dynamics: non-denaturing high-pressure effect on lysozyme in solution. J R Soc Interface 6(Suppl 5):S619–634PubMedPubMedCentralCrossRefGoogle Scholar
  93. Pallavi R, Roy N, Nageshan RK, Talukdar P, Pavithra SR, Reddy R, Venketesh S, Kumar R, Gupta AK, Singh RK, Yadav SC, Tatu U (2010) Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. J Biol Chem 285:37964–37975PubMedPubMedCentralCrossRefGoogle Scholar
  94. Panaretou B, Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1998) ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J 17:4829–4836PubMedPubMedCentralCrossRefGoogle Scholar
  95. Panaretou B, Siligardi G, Meyer P, Maloney A, Sullivan JK, Singh S, Millson SH, Clarke PA, Naaby-Hansen S, Stein R, Cramer R, Mollapour M, Workman P, Piper PW, Pearl LH, Prodromou C (2002) Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol Cell 10:1307–1318PubMedCrossRefGoogle Scholar
  96. Partridge JR, Lavery LA, Elnatan D, Naber N, Cooke R, Agard DA (2014) A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity. eLife 3Google Scholar
  97. Patki JM, Pawar SS (2013) HSP90: chaperone-me-not. Pathol Oncol Res 19:631–640PubMedCrossRefGoogle Scholar
  98. Pierpaoli EV, Sandmeier E, Schonfeld HJ, Christen P (1998) Control of the DnaK chaperone cycle by substoichiometric concentrations of the co-chaperones DnaJ and GrpE. J Biol Chem 273:6643–6649PubMedCrossRefGoogle Scholar
  99. Pullen L, Bolon DN (2011) Enforced N-domain proximity stimulates Hsp90 ATPase activity and is compatible with function in vivo. J Biol Chem 286:11091–11098PubMedPubMedCentralCrossRefGoogle Scholar
  100. Putnam CD, Hammel M, Hura GL, Tainer JA (2007) X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution. Q Rev Biophys 40:191–285PubMedCrossRefGoogle Scholar
  101. Rambo RP, Tainer JA (2010) Bridging the solution divide: comprehensive structural analyses of dynamic RNA, DNA, and protein assemblies by small-angle X-ray scattering. Curr Opin Struct Biol 20:128–137PubMedPubMedCentralCrossRefGoogle Scholar
  102. Rambo RP, Tainer JA (2011) Characterizing flexible and intrinsically unstructured biological macromolecules by SAS using the Porod-Debye law. Biopolymers 95(8):559–571PubMedPubMedCentralCrossRefGoogle Scholar
  103. Ramos CHI, Oliveira CLP, Fan CY, Torriani IL, Cyr DM (2008) Conserved central domains control the quaternary structure of type I and type II Hsp40 molecular chaperones. J Mol Biol 383:155–166PubMedPubMedCentralCrossRefGoogle Scholar
  104. Ran QT, Wadhwa R, Kawai R, Kaul SC, Sifers RN, Bick RJ, Smith JR, Pereira-Smith OM (2000) Extramitochondrial localization of mortalin/mthsp70/PBP74/GRP75. Biochem Biophys Res Comm 275:174–179PubMedCrossRefGoogle Scholar
  105. Ratzke C, Nguyen MN, Mayer MP, Hugel T (2012) From a ratchet mechanism to random fluctuations evolution of Hsp90’s mechanochemical cycle. J Mol Biol 423:462–471PubMedCrossRefGoogle Scholar
  106. Retzlaff M, Hagn F, Mitschke L, Hessling M, Gugel F, Kessler H, Richter K, Buchner J (2010) Asymmetric activation of the Hsp90 dimer by its cochaperone Aha1. Mol Cell 37:344–354PubMedCrossRefGoogle Scholar
  107. Richter K, Soroka J, Skalniak L, Leskovar A, Hessling M, Reinstein J, Buchner J (2008) Conserved conformational changes in the ATPase cycle of human Hsp90. J Biol Chem 283:17757–17765PubMedCrossRefGoogle Scholar
  108. Rudiger S, Schneider-Mergener J, Bukau B (2001) Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone. EMBO J 20:1042–1050PubMedPubMedCentralCrossRefGoogle Scholar
  109. Seraphim TV, Alves MM, Silva IM, Gomes FE, Silva KP, Murta SM, Barbosa LR, Borges JC (2013) Low resolution structural studies indicate that the activator of Hsp90 ATPase 1 (Aha1) of Leishmania braziliensis has an elongated shape which allows its interaction with both N- and M-domains of Hsp90. PLoS ONE 8:e66822PubMedPubMedCentralCrossRefGoogle Scholar
  110. Seraphim TV, Ramos CHI, Borges JC (2014) The interaction networks of Hsp70 and Hsp90 in the Plasmodium and Leishmania parasites. In: The molecular chaperones interaction networks in protein folding and degradation, vol 1, Interactomics and systems biology. Springer, New York, pp 445–481Google Scholar
  111. Seraphim TV, Gava LM, Mokry DZ, Cagliari TC, Barbosa LRS, Ramos CHI, Borges JC (2015) The C-terminal region of the human p23 chaperone modulates its structure and function. Arch Biochem Biophys 565:57–67PubMedCrossRefGoogle Scholar
  112. Sha BD, Lee S, Cyr DM (2000) The crystal structure of the peptide-binding fragment from the yeast Hsp40 protein Sis1. Structure 8:799–807PubMedCrossRefGoogle Scholar
  113. Shonhai A, Maier AG, Przyborski JM, Blatch GL (2011) Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis. Protein Pept Lett 18:143–157PubMedCrossRefGoogle Scholar
  114. Sichting M, Mokranjac D, Azem A, Neupert W, Hell K (2005) Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1. EMBO J 24:1046–1056PubMedPubMedCentralCrossRefGoogle Scholar
  115. Silva JC, Borges JC, Cyr DM, Ramos CHI, Torriani IL (2011) Central domain deletions affect the SAXS solution structure and function of Yeast Hsp40 proteins Sis1 and Ydj1. BMC Struct Biol 11:40PubMedPubMedCentralCrossRefGoogle Scholar
  116. Silva KP, Seraphim TV, Borges JC (2013) Structural and functional studies of Leishmania braziliensis Hsp90. Biochim Biophys Acta 1834:351–361PubMedCrossRefGoogle Scholar
  117. Sondheimer N, Lopez N, Craig EA, Lindquist S (2001) The role of Sis1 in the maintenance of the [RNQ(+)] prion. EMBO J 20:2435–2442PubMedPubMedCentralCrossRefGoogle Scholar
  118. Southworth DR, Agard DA (2008) Species-dependent ensembles of conserved conformational states define the Hsp90 chaperone ATPase cycle. Mol Cell 32(5):631–640Google Scholar
  119. Spinozzi F, Ferrero C, Ortore MG, De Maria Antolinos A, Mariani P (2014) GENFIT: software for the analysis of small-angle X-ray and neutron scattering data of macromolecules in solution. J Appl Cryst 47:1132–1139CrossRefGoogle Scholar
  120. Street TO, Krukenberg KA, Rosgen J, Bolen DW, Agard DA (2010) Osmolyte-induced conformational changes in the Hsp90 molecular chaperone. Protein Sci 19:57–65PubMedPubMedCentralGoogle Scholar
  121. Street TO, Lavery LA, Agard DA (2011) Substrate binding drives large-scale conformational changes in the Hsp90 molecular chaperone. Mol Cell 42:96–105PubMedPubMedCentralCrossRefGoogle Scholar
  122. Summers DW, Douglas PM, Ramos CHI, Cyr DM (2009) Polypeptide transfer from Hsp40 to Hsp70 molecular chaperones. Trends Biochem Sci 34:230–233PubMedPubMedCentralCrossRefGoogle Scholar
  123. Sun L, Prince T, Manjarrez JR, Scroggins BT, Matts RL (2012) Characterization of the interaction of Aha1 with components of the Hsp90 chaperone machine and client proteins. Biochim Biophys Acta 1823:1092–1101PubMedCrossRefGoogle Scholar
  124. Sun L, Hartson SD, Matts RL (2015) Identification of proteins associated with Aha1 in HeLa cells by quantitative proteomics. Biochim Biophys Acta 1854:365–380PubMedCrossRefGoogle Scholar
  125. Svergun DI (1992) Determination of the regularization parameter in indirect-transform methods using perceptual criteria. J Appl Cryst 25:495–503CrossRefGoogle Scholar
  126. Svergun DI (1999) Restoring low resolution structure of biological macromolecules from solution scattering using simulated annealing. Biophys J 76:2879–2886PubMedPubMedCentralCrossRefGoogle Scholar
  127. Svergun DI (2015) Svergun’s group web page. http://www.embl-hamburg.de/research/unit/svergun/index.html
  128. Svergun DI, Feĭgin LA, Taylor GW (1987) Structure analysis by small-angle X-ray and neutron scattering. Plenum, New YorkGoogle Scholar
  129. Svergun D, Barberato C, Koch MHJ (1995) CRYSOL—a program to evaluate x-ray solution scattering of biological macromolecules from atomic coordinates. J Appl Cryst 28:768–773CrossRefGoogle Scholar
  130. Szabo A, Langer T, Schroder H, Flanagan J, Bukau B, Hartl FU (1994) The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system—DnaK, DnaJ, and GrpE. Proc Natl Acad Sci U S A 91:10345–10349PubMedPubMedCentralCrossRefGoogle Scholar
  131. Szklarz LKS, Guiard B, Rissler M, Wiedemann N, Kozjak V, van der Laan M, Lohaus C, Marcus K, Meyer HE, Chacinska A, Pfanner N, Meisinger C (2005) Inactivation of the mitochondrial heat shock protein Zim17 leads to aggregation of matrix Hsp70s followed by plelotropic effects on morphology and protein biogenesis. J Mol Biol 351:206–218CrossRefGoogle Scholar
  132. Szyperski T, Pellecchia M, Wall D, Georgopoulos C, Wuthrich K (1994) NMR structure determination of the Escherichia coli DnaJ molecular chaperone: secondary structure and backbone fold of the N-terminal region (residues-2-108) containing the highly conserved J domain. Proc Natl Acad Sci U S A 91:11343–11347PubMedPubMedCentralCrossRefGoogle Scholar
  133. Tompa P (2005) The interplay between structure and function in intrinsically unstructured proteins. FEBS Lett 579:3346–3354PubMedCrossRefGoogle Scholar
  134. Tompa P (2011) Unstructural biology coming of age. Curr Opin Struct Biol 21:419–425PubMedCrossRefGoogle Scholar
  135. Tompa P, Csermely P (2004) The role of structural disorder in the function of RNA and protein chaperones. FASEB J 18:1169–1175PubMedCrossRefGoogle Scholar
  136. Tria G, Mertens HDT, Kachala M, Svergun DI (2015) Advanced ensemble modelling of flexible macromolecules using X-ray solution scattering. IUCrJ 2:207–217PubMedPubMedCentralCrossRefGoogle Scholar
  137. Trudeau T, Nassar R, Cumberworth A, Wong ETC, Woollard G, Gsponer J (2013) Structure and intrinsic disorder in protein autoinhibition. Structure 21:332–341PubMedCrossRefGoogle Scholar
  138. Uversky VN, Gillespie JR, Fink AL (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41:415–427PubMedCrossRefGoogle Scholar
  139. Volkov VV, Svergun DI (2003) Uniqueness of ab initio shape determination in small-angle scattering. J Appl Cryst 36:860–864CrossRefGoogle Scholar
  140. Vu MT, Zhai P, Lee J, Guerra C, Liu S, Gustin MC, Silberg JJ (2012) The DNLZ/HEP zinc-binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9. Protein Sci 21:258–267PubMedPubMedCentralCrossRefGoogle Scholar
  141. Wadhwa R, Kaul SC, Mitsui Y, Sugimoto Y (1993) Differential subcellular-distribution of mortalin in mortal and immortal mouse and human fibroblasts. Exp Cell Res 207:442–448PubMedCrossRefGoogle Scholar
  142. Wang ML, Kurland CG, Caetano-Anolles G (2011) Reductive evolution of proteomes and protein structures. Proc Natl Acad Sci U S A 108:11954–11958PubMedPubMedCentralCrossRefGoogle Scholar
  143. Weaver AJ, Sullivan WP, Felts SJ, Owen BAL, Toft DO (2000) Crystal structure and activity of human p23, a heat shock protein 90 co-chaperone. J Biol Chem 275:23045–23052PubMedCrossRefGoogle Scholar
  144. Weikl T, Abelmann K, Buchner J (1999) An unstructured C-terminal region of the Hsp90 co-chaperone p23 is important for its chaperone function. J Mol Biol 293:685–691PubMedCrossRefGoogle Scholar
  145. Woo SH, An S, Lee HC, Jin HO, Seo SK, Yoo DH, Lee KH, Rhee CH, Choi EJ, Hong SI, Park IC (2009) A truncated form of p23 down-regulates telomerase activity via disruption of Hsp90 function. J Biol Chem 284:30871–30880PubMedPubMedCentralCrossRefGoogle Scholar
  146. Worrall LJ, Wear MA, Page AP, Walkinshaw MD (2008) Cloning, purification and characterization of the Caenorhabditis elegans small glutamine-rich tetratricopeptide repeat-containing protein. Biochim Biophys Acta 1784:496–503PubMedCrossRefGoogle Scholar
  147. Yamamoto H, Momose T, Yatsukawa Y, Ohshima C, Ishikawa D, Sato T, Tamura Y, Ohwa Y, Endo T (2005) Identification of a novel member of yeast mitochondrial Hsp70-associated motor and chaperone proteins that facilitates protein translocation across the inner membrane. FEBS Lett 579:507–511PubMedCrossRefGoogle Scholar
  148. Yan W, Craig EA (1999) The glycine-phenylalanine-rich region determines the specificity of the yeast Hsp40 Sis1. Mol Cell Biol 19:7751–7758PubMedPubMedCentralCrossRefGoogle Scholar
  149. Young JC, Hartl FU (2000) Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the co-chaperone p23. EMBO J 19:5930–5940PubMedPubMedCentralCrossRefGoogle Scholar
  150. Young JC, Moarefi I, Hartl FU (2001) Hsp90: a specialized but essential protein-folding tool. J Cell Biol 154:267–273PubMedPubMedCentralCrossRefGoogle Scholar
  151. Zhai P, Stanworth C, Liu S, Silberg JJ (2008) The human escort protein hep binds to the ATPase domain of mitochondrial Hsp70 and regulates ATP hydrolysis. J Biol Chem 283:26098–26106PubMedPubMedCentralCrossRefGoogle Scholar
  152. Zhao R, Houry WA (2005) Hsp90: a chaperone for protein folding and gene regulation. Biochem Cell Biol 83:703–710PubMedCrossRefGoogle Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Instituto de Química de São CarlosUniversidade de São PauloSão CarlosBrazil
  2. 2.Instituto de FísicaUniversidade de São PauloSão PauloBrazil

Personalised recommendations