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Cited by 196Heat shock proteins researchProtein Structure and DynamicsUbiquitin and proteasome pathways

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The Co-chaperone p23 Arrests the Hsp90 ATPase Cycle to Trap Client Proteins

McLaughlin, Stephen H., Sobott, Frank, Yao, Zhong-ping, Zhang, Wei, Nielsen, Peter R., Grossmann, J. Günter, Laue, Ernest D., Robinson, Carol V., Jackson, Sophie E.·2006·Journal of Molecular Biology
DOI 10.1016/j.jmb.2005.11.085
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Abstract

The action of the molecular chaperone Hsp90 is essential for the activation and assembly of an increasing number of client proteins. This function of Hsp90 has been proposed to be governed by conformational changes driven by ATP binding and hydrolysis. Association of co-chaperones and client proteins regulate the ATPase activity of Hsp90. Here, we have examined the inhibition of the ATPase activity of human Hsp90beta by one such co-chaperone, human p23. We demonstrate that human p23 interacts with Hsp90 in both the absence and presence of nucleotide with a higher affinity in the presence of the ATP analogue AMP-PNP. This is consistent with an analysis of the effect of p23 on the steady-state kinetics that revealed a mixed mechanism of inhibition. Mass spectrometry of the intact Hsp90.p23 complex determined the stoichiometry of binding to be one p23 to each subunit of the Hsp90 dimer. p23 was also shown to interact with a monomeric, truncated fragment of Hsp90, lacking the C-terminal homodimerisation domain, indicating dimerisation of Hsp90 is not a prerequisite for association with p23. Complex formation between Hsp90 and p23 increased the apparent affinity of Hsp90 for AMP-PNP and completely inhibited the ATPase activity. We propose a model where the role of p23 is to lock individual subunits of Hsp90 in an ATP-dependent conformational state that has a high affinity for client proteins.

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Research works printed but not linked: 45

  1. Mayer, 1999, Molecular chaperones: the busy life of Hsp90, Curr. Biol., 9, R322, 10.1016/S0960-9822(99)80203-6 · DOI
  2. Wegele, 2004, Hsp70 and Hsp90-a relay team for protein folding, Rev. Physiol. Biochem. Pharmacol., 151, 1, 10.1007/s10254-003-0021-1 · DOI
  3. Pratt, 1998, The Hsp90-based chaperone system: involvement in signal transduction from a variety of hormone and growth factor receptors, Proc. Soc. Expt. Biol. Med., 217, 420, 10.3181/00379727-217-44252 · DOI
  4. Picard, 2002, Heat-shock protein 90, a chaperone for folding and regulation, Cell Mol. Life Sci., 59, 1640, 10.1007/PL00012491 · DOI
  5. Young, 2001, Hsp90: a specialized but essential protein-folding tool, J. Cell Biol., 154, 267, 10.1083/jcb.200104079 · DOI
  6. Zhao, 2005, Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the Hsp90 chaperone, Cell, 120, 715, 10.1016/j.cell.2004.12.024 · DOI · Paper page
  7. Prodromou, 1997, Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone, Cell, 90, 65, 10.1016/S0092-8674(00)80314-1 · DOI
  8. Obermann, 1998, In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis, J. Cell Biol., 143, 901, 10.1083/jcb.143.4.901 · DOI
  9. Prodromou, 2000, The ATPase cycle of Hsp90 drives a molecular ‘clamp’ via transient dimerization of the N-terminal domains, EMBO J., 19, 4383, 10.1093/emboj/19.16.4383 · DOI · Paper page
  10. Sullivan, 1997, Nucleotides and two functional states of Hsp90, J. Biol. Chem., 272, 8007, 10.1074/jbc.272.12.8007 · DOI
  11. Young, 2000, Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the co-chaperone p23, EMBO J., 19, 5930, 10.1093/emboj/19.21.5930 · DOI
  12. McLaughlin, 2002, Stimulation of the weak ATPase activity of human Hsp90 by a client protein, J. Mol. Biol., 315, 787, 10.1006/jmbi.2001.5245 · DOI
  13. McLaughlin, 2004, Independent ATPase activity of Hsp90 subunits creates a flexible assembly platform, J. Mol. Biol., 344, 813, 10.1016/j.jmb.2004.09.055 · DOI
  14. Richter, 2003, Sti1 is a non-competitive inhibitor of the Hsp90 ATPase. Binding prevents the N-terminal dimerization reaction during the ATPase cycle, J. Biol. Chem., 278, 10328, 10.1074/jbc.M213094200 · DOI
  15. Siligardi, 2002, Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37, J. Biol. Chem., 277, 20151, 10.1074/jbc.M201287200 · DOI
  16. Zhang, 2004, Biochemical and structural studies of the interaction of Cdc37 with Hsp90, J. Mol. Biol., 340, 891, 10.1016/j.jmb.2004.05.007 · DOI
  17. Johnson, 1994, Characterization of a novel 23-kilodalton protein of unactive progesterone receptor complexes, Mol. Cell. Biol., 14, 1956, 10.1128/MCB.14.3.1956 · DOI
  18. Johnson, 1994, A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23, J. Biol. Chem., 269, 24989, 10.1016/S0021-9258(17)31487-4 · DOI
  19. Hutchison, 1995, The 23-kDa acidic protein in reticulocyte lysate is the weakly bound component of the hsp foldosome that is required for assembly of the glucocorticoid receptor into a functional heterocomplex with Hsp90, J. Biol. Chem., 270, 18841, 10.1074/jbc.270.32.18841 · DOI
  20. Toft, 1998, Recent advances in the study of Hsp90 structure and mechanism of action, Trends Endocrinol. Metab., 9, 238, 10.1016/S1043-2760(98)00060-5 · DOI
  21. Smith, 2000, Chaperones in progesterone receptor complexes, Semin. Cell Dev. Biol., 11, 45, 10.1006/scdb.1999.0350 · DOI
  22. Dittmar, 1997, Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based chaperone machinery. The role of p23 is to stabilize receptor.hsp90 heterocomplexes formed by hsp90.p60.hsp70, J. Biol. Chem., 272, 21213, 10.1074/jbc.272.34.21213 · DOI
  23. Kosano, 1998, The assembly of progesterone receptor-Hsp90 complexes using purified proteins, J. Biol. Chem., 273, 32973, 10.1074/jbc.273.49.32973 · DOI
  24. Bose, 1996, Chaperone function of Hsp90-associated proteins, Science, 274, 1715, 10.1126/science.274.5293.1715 · DOI
  25. Fang, 1998, SBA1 encodes a yeast hsp90 cochaperone that is homologous to vertebrate p23 proteins, Mol. Cell. Biol., 18, 3727, 10.1128/MCB.18.7.3727 · DOI
  26. Zhu, 2004, Evolutionary epitopes of Hsp90 and p23: implications for their interaction, FASEB J., 18, 940, 10.1096/fj.04-1570hyp · DOI
  27. Oxelmark, 2003, Genetic dissection of p23, an Hsp90 cochaperone, reveals a distinct surface involved in estrogen receptor signaling, J. Biol. Chem., 278, 36547, 10.1074/jbc.M305960200 · DOI
  28. Wochnik, 2004, Inhibition of GR-mediated transcription by p23 requires interaction with Hsp90, FEBS Letters, 560, 35, 10.1016/S0014-5793(04)00066-3 · DOI
  29. Chadli, 2000, Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90, Proc. Natl Acad. Sci. USA, 97, 12524, 10.1073/pnas.220430297 · DOI
  30. Harris, 2004, The crystal structure of the carboxy-terminal dimerization domain of hptG, the Escherichia coli Hsp90, reveals apotential substrate binding site, Structure, 12, 1087, 10.1016/j.str.2004.03.020 · DOI
  31. Grenert, 1999, The importance of ATP binding and hydrolysis by Hsp90 in formation and function of protein heterocomplexes, J. Biol. Chem., 274, 17525, 10.1074/jbc.274.25.17525 · DOI
  32. Wigley, 1991, Crystal structure of an N-terminal fragment of the DNA gyrase B protein, Nature, 351, 624, 10.1038/351624a0 · DOI
  33. Richter, 2001, Coordinated ATP hydrolysis by the Hsp90 dimer, J. Biol. Chem., 276, 33689, 10.1074/jbc.M103832200 · DOI
  34. Huai, 2005, Structures of the N-terminal and middle domains of E.coli Hsp90 and conformation changes upon ADP binding, Structure, 13, 579, 10.1016/j.str.2004.12.018 · DOI
  35. Roe, 2004, The mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(Cdc37), Cell, 116, 87, 10.1016/S0092-8674(03)01027-4 · DOI
  36. Harst, 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, 10.1042/BJ20041283 · DOI
  37. Hartson, 2000, p50cdc37 is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules, Biochemistry, 39, 7631, 10.1021/bi000315r · DOI
  38. Meyer, 2004, Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery, EMBO J., 23, 1402, 10.1038/sj.emboj.7600141 · DOI
  39. Abbas-Terki, 2002, The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically, Biol. Chem., 383, 1335, 10.1515/BC.2002.152 · DOI
  40. Prodromou, 1999, Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones, EMBO J., 18, 754, 10.1093/emboj/18.3.754 · DOI
  41. Sobott, 2002, A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies, Anal. Chem., 74, 1402, 10.1021/ac0110552 · DOI · Paper page
  42. Sobott, 2002, Protein complexes gain momentum, Curr. Opin. Struct. Biol., 12, 729, 10.1016/S0959-440X(02)00400-1 · DOI
  43. Heck, 2004, Investigation of intact protein complexes by mass spectrometry, Mass Spectrom. Rev., 23, 368, 10.1002/mas.10081 · DOI
  44. Kebarle, 2000, A brief overview of the present status of the mechanisms involved in electrospray mass spectrometry, J. Mass Spectrom., 35, 804, 10.1002/1096-9888(200007)35:7<804::AID-JMS22>3.0.CO;2-Q · DOI
  45. Brune, 1998, Mechanism of inorganic phosphate interaction with phosphate binding protein from Escherichia coli, Biochemistry, 37, 10370, 10.1021/bi9804277 · DOI

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Metadata

Authors
McLaughlin, S. H., Sobott, F., Yao, Z.-P., Zhang, W., Nielsen, P. R., Grossmann, J. G., Laue, E. D., Robinson, C. V., & Jackson, S. E.
Affiliations
  • University of Cambridge (GB)
  • Daresbury Laboratory (GB)
Corresponding author
  • McLaughlin, Stephen H.
  • Jackson, Sophie E.
ORCID
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2006-02
Volume
356
Issue
3
Pages
746-758
ISSN
0022-2836 (ISSN-L)
DOI
10.1016/j.jmb.2005.11.085
OpenAlex
W2070981149
Cited by
196
References
57
Citations by year
2026: 5 · 2025: 6 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 3 · 2018: 10 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 14 · 2013: 14 · 2012: 15
FWCI
3.15
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Leverhulme Trust
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
HSP90, p23, co-chaperones, ATPase activity, HSP90β, AMP-PNP, mixed-type inhibition, protein-protein interaction, ATP binding, chaperone mechanism
MeSH terms
Adenosine Triphosphatases, Adenylyl Imidodiphosphate, Calorimetry, Chromatography, Gel, DNA-Binding Proteins, Humans, Kinetics, Protein Binding, Protein Conformation, Thermodynamics, Molecular Chaperones, HSP90 Heat-Shock Proteins, Dimerization, Protein Subunits

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