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

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1016/j.jmb.2005.11.085

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Structural and Functional Analysis of the Middle Segment of Hsp90: Implications for ATP Hydrolysis and Client Protein and Cochaperone Interactions
Meyer, P., Prodromou, C., Hu, B., Vaughan, C., Roe, S. M., Panaretou, B., Piper, P. W., & Pearl, L. H. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00065-0 · Cited by 491
Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin Cyp-40 and the Steroid Aporeceptor-Associated Protein p23
Freeman, B. C., Toft, D. O., & Morimoto, R. I. (1996) · Science · doi:10.1126/science.274.5293.1718 · Cited by 370
Binding of p23 and hsp90 during assembly with the progesterone receptor.
Johnson, J. L., & Toft, D. O. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.6.8592513 · Cited by 233
Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle
Siligardi, G., Hu, B., Panaretou, B., Piper, P. W., Pearl, L. H., & Prodromou, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410562200 · Cited by 207 · cited 6×
“In sharp contrast to human p23, Sba1 inhibits the ATPase activity of yeast Hsp90 only partially.(33,34) The level of sequence identity is 27% in the globular cores of human and yeast p23 compared to 64% identity for the respective Hsp90 homologues.”
BackgroundMethodResultInfluential
A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p).
Millson, S. H., Truman, A. W., King, V., Prodromou, C., Pearl, L. H., & Piper, P. W. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.5.849-860.2005 · Cited by 172
The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies
Freeman, B. C., Felts, S. J., Toft, D. O., & Yamamoto, K. R. (2000) · Genes & Development · doi:10.1101/gad.14.4.422 · Cited by 168 · cited 1×
“Opposing a role in assisting the assembly process, p23 may alter the transcriptional activity of nuclear receptors by affecting the dissociation rate of the receptor–DNA response element complex.(28) The molecular mechanism by which p23 acts as a co-chaperone for Hsp90 is unknown.”
Background
The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle
Richter, K., Walter, S., & Buchner, J. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.07.064 · Cited by 159 · cited 12×
“In sharp contrast to human p23, Sba1 inhibits the ATPase activity of yeast Hsp90 only partially.(33,34) The level of sequence identity is 27% in the globular cores of human and yeast p23 compared to 64% identity for the respective Hsp90 homologues.”
BackgroundMethodResultInfluential
Crystal Structure and Activity of Human p23, a Heat Shock Protein 90 Co-chaperone
Weaver, A. J., Sullivan, W. P., Felts, S. J., Owen, B. A. L., & Toft, D. O. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003410200 · Cited by 136
Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction
Knoblauch, R., & Garabedian, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3748 · Cited by 126
The Influence of ATP and p23 on the Conformation of hsp90
Sullivan, W. P., Owen, B. A. L., & Toft, D. O. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207754200 · Cited by 111

Flagged first, then by citations

Show all 12 references

Research works printed but not linked: 45

Mayer, 1999, Molecular chaperones: the busy life of Hsp90, Curr. Biol., 9, R322, 10.1016/S0960-9822(99)80203-6 · DOI
Wegele, 2004, Hsp70 and Hsp90-a relay team for protein folding, Rev. Physiol. Biochem. Pharmacol., 151, 1, 10.1007/s10254-003-0021-1 · DOI
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
Picard, 2002, Heat-shock protein 90, a chaperone for folding and regulation, Cell Mol. Life Sci., 59, 1640, 10.1007/PL00012491 · DOI
Young, 2001, Hsp90: a specialized but essential protein-folding tool, J. Cell Biol., 154, 267, 10.1083/jcb.200104079 · DOI
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
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
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
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
Sullivan, 1997, Nucleotides and two functional states of Hsp90, J. Biol. Chem., 272, 8007, 10.1074/jbc.272.12.8007 · DOI
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
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
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
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
Siligardi, 2002, Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37, J. Biol. Chem., 277, 20151, 10.1074/jbc.M201287200 · DOI
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
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
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
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
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
Smith, 2000, Chaperones in progesterone receptor complexes, Semin. Cell Dev. Biol., 11, 45, 10.1006/scdb.1999.0350 · DOI
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
Kosano, 1998, The assembly of progesterone receptor-Hsp90 complexes using purified proteins, J. Biol. Chem., 273, 32973, 10.1074/jbc.273.49.32973 · DOI
Bose, 1996, Chaperone function of Hsp90-associated proteins, Science, 274, 1715, 10.1126/science.274.5293.1715 · DOI
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
Zhu, 2004, Evolutionary epitopes of Hsp90 and p23: implications for their interaction, FASEB J., 18, 940, 10.1096/fj.04-1570hyp · DOI
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
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
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
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
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
Wigley, 1991, Crystal structure of an N-terminal fragment of the DNA gyrase B protein, Nature, 351, 624, 10.1038/351624a0 · DOI
Richter, 2001, Coordinated ATP hydrolysis by the Hsp90 dimer, J. Biol. Chem., 276, 33689, 10.1074/jbc.M103832200 · DOI
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
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
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
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
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
Abbas-Terki, 2002, The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically, Biol. Chem., 383, 1335, 10.1515/BC.2002.152 · DOI
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
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
Sobott, 2002, Protein complexes gain momentum, Curr. Opin. Struct. Biol., 12, 729, 10.1016/S0959-440X(02)00400-1 · DOI
Heck, 2004, Investigation of intact protein complexes by mass spectrometry, Mass Spectrom. Rev., 23, 368, 10.1002/mas.10081 · DOI
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
Brune, 1998, Mechanism of inorganic phosphate interaction with phosphate binding protein from Escherichia coli, Biochemistry, 37, 10370, 10.1021/bi9804277 · DOI

Sorted by citations

Items 101–182 of 182

A review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering
Borges, J. C., Seraphim, T. V., Dores-Silva, P. R., & Barbosa, L. R. S. (2016) · Biophysical Reviews · doi:10.1007/s12551-016-0194-x · Cited by 32
“This interaction allows p23 to regulate Hsp90 function by inhibiting its ATPase activity (McLaughlin et al. 2006); however, the exact role of this inhibition remains controversial.”
Background
p23 and Aha1
Rehn, A., & Büchner, J. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_6 · Cited by 31
Structural and Computational Biology of the Molecular Chaperone Hsp90: From Understanding Molecular Mechanisms to Computer-Based Inhibitor Design
Verkhivker, G. M., Dixit, A., Morra, G., & Colombo, G. (2009) · Current Topics in Medicinal Chemistry · doi:10.2174/156802609789895700 · Cited by 22
“p23/Sba1 activates ATPase by stabilizing the closed conformation of the lid [51-53].”
Background
NudCL2 is an Hsp90 cochaperone to regulate sister chromatid cohesion by stabilizing cohesin subunits
Yang, Y., Wang, W., Li, M., Gao, Y., Zhang, W., Huang, Y., Zhuo, W., Yan, X., Liu, W., Wang, F., et al. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2957-y · Cited by 26
Self-citation
Characterization of plant p23-like proteins for their co-chaperone activities
Zhang, Z., Sullivan, W., Felts, S. J., Prasad, B. D., Toft, D. O., & Krishna, P. (2010) · Cell Stress and Chaperones · doi:10.1007/s12192-010-0182-1 · Cited by 27
“This is achieved, in part, through interactions with several surfaces of the Hsp90 N terminus and regions beyond the charged domain (Chadli et al. 2000; Ali et al. 2006) and results in an inhibition of the ATPase activity of Hsp90 (Richter et al. 2004; Ali et al. 2006; McLaughlin et al. 2006 ).”
BackgroundInfluential
Dual Roles for Yeast Sti1/Hop in Regulating the Hsp90 Chaperone Cycle
Reidy, M., Kumar, S., Anderson, D. E., & Masison, D. C. (2018) · Genetics · doi:10.1534/genetics.118.301178 · Cited by 22
“2017), and Sba1 prolongs client interactions by binding an NTD-closed state of Hsp90 (McLaughlin et al. 2006).”
Background
Large Rotation of the N-terminal Domain of Hsp90 Is Important for Interaction with Some but Not All Client Proteins
Daturpalli, S., Knieß, R. A., Lee, C.-T., & Mayer, M. P. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.03.025 · Cited by 23
Reconstructing the Hsp90/Tau Machine
Jinwal, U. K., Koren, J., & Dickey, C. A. (2013) · Current Enzyme Inhibition · doi:10.2174/1573408011309010006 · Cited by 23
“The protein P23 is required for Hsp90 ATPase activity, and thus refolding activity [35].”
Background
Characterization of Plasmodium falciparum co-chaperone p23: its intrinsic chaperone activity and interaction with Hsp90
Chua, C.-S., Low, H., Goo, K., & Sim, T. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0275-0 · Cited by 22
“The observation is consistent with that reported for the human and yeast homologues [10, 11, 52], and it was suggested”
BackgroundResult
A survey of the year 2006 literature on applications of isothermal titration calorimetry
Okhrimenko, O., & Jelesarov, I. (2008) · Journal of Molecular Recognition · doi:10.1002/jmr.859 · Cited by 36
Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90
Vollmar, L., Schimpf, J., Hermann, B. A., & Hugel, T. (2024) · Nature Communications · doi:10.1038/s41467-024-44847-6 · Cited by 24
Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils
Prasanna, P., & Upadhyay, A. (2020) · Infection and Immunity · doi:10.1128/iai.00559-20 · Cited by 21
“aggregation of denatured proteins (101, 102).”
Identification of two p23 co‐chaperone isoforms in Leishmania braziliensis exhibiting similar structures and Hsp90 interaction properties despite divergent stabilities
Batista, F. A. H., Almeida, G. S., Seraphim, T. V., Silva, K. P., Murta, S. M. F., Barbosa, L. R. S., & Borges, J. C. (2014) · FEBS Journal · doi:10.1111/febs.13141 · Cited by 20
Effects of inhibitors on Hsp90's conformational dynamics, cochaperone and client interactions
Schmid, S., Götz, M., & Hugel, T. (2018) · bioRxiv · doi:10.1101/255190 · Cited by 19
“Second, we investigate the in vitro effect of the inhibitors on the binding of two well characterized cochaperones, namely p23 ( McLaughlin et al., 2006 ) and Aha1 ( Li et al., 2013 ) using fluorescence anisotropy.”
BackgroundMethod
A Multicolor Single-Molecule FRET Approach to Study Protein Dynamics and Interactions Simultaneously.
Götz, M., Wortmann, P., Schmid, S., & Hugel, T. (2016) · Methods in Enzymology · doi:10.1016/bs.mie.2016.08.024 · Cited by 19
The Interaction Networks of Hsp70 and Hsp90 in the Plasmodium and Leishmania Parasites
Seraphim, T. V., Ramos, C. H. I., & Borges, J. C. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1130-1_17 · Cited by 28
Mechanism of chaperone recruitment and retention on mitochondrial precursors
Juszkiewicz, S., Peak‐Chew, S., & Hegde, R. S. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e25-01-0035 · Cited by 20
“…that p23 is important for the efﬁcient buffering of mitochondrial precursors by Hsp90 during mitochondrial import stress, presumably by slowing down the Hsp90 cycle (McLaughlin et al. , 2006; Noddings et al. , 2022) and effectively preventing the precursors from reaching their native folded state.”
Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co‐chaperone p23 as potential anticancer agent
Bharadwaj, S., Lee, K. E., Dwivedi, V. D., Yadava, U., & Kang, S. G. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29229 · Cited by 19
“It was first identified as component of the mature progesterone receptor complexes(2) and later predicted to act as a co‐ chaperone that provide stability to ATP‐bound form of heat shock protein 90 (Hsp90), and thereby, stabilizing the Hsp90 interactions with steroid receptors.(3) Besides, it was reported to support H…”
Background
Toxoplasma gondii: a bradyzoite-specific DnaK-tetratricopeptide repeat (DnaK-TPR) protein interacts with p23 co-chaperone protein.
Ueno, A., Dautu, G., Haga, K., Munyaka, B., Carmen, G., Kobayashi, Y., & Igarashi, M. (2011) · Experimental parasitology · doi:10.1016/j.exppara.2011.01.015 · Cited by 18
Characterization of orchardgrass p23, a flowering plant Hsp90 cohort protein
Cha, J., Ermawati, N., Jung, M. H., Su’udi, M., Kim, K.-Y., Kim, J., Han, C., Lee, K. H., & Son, D. (2008) · Cell Stress and Chaperones · doi:10.1007/s12192-008-0077-6 · Cited by 16
“After binding to Hsp90, p23 stabilizes the conformational state of Hsp90 by inhibition of ATP hydrolysis (McLaughlin et al. 2006).”
Background
Characterization of three heat shock protein 70 genes from Liriomyza trifolii and expression during thermal stress and insect development.
Chang, Y.-W., Zhang, X.-X., Chen, J.-Y., Lu, M.-X., Gong, W., & Du, Y.-Z. (2019) · Bulletin of entomological research · doi:10.1017/s0007485318000354 · Cited by 17
Co-chaperones of Hsp90 inPlasmodium falciparumand their concerted roles in cellular regulation
Chua, C., Low, H., & Sim, T. (2014) · Parasitology · doi:10.1017/s0031182013002084 · Cited by 19
“In vitro experiments indicated that the co-chaperone p23 only binds to Hsp90 in the ATPbound state and its interaction slows the ATP hydrolysis of Hsp90 (McLaughlin et al. 2006).”
Background
Molecular Chaperones: Structure-Function Relationship and their Role in Protein Folding
Chatterjee, B. K., Puri, S., Sharma, A. K., Pastor, A., & Chaudhuri, T. K. (2018) · Heat shock proteins · doi:10.1007/978-3-319-74715-6_8 · Cited by 21
Targeting Chaperone/Co-Chaperone Interactions with Small Molecules: A Novel Approach to Tackle Neurodegenerative Diseases
Wang, L., Bergkvist, L., Kumar, R., Winblad, B. G., & Pavlov, P. F. (2021) · Cells · doi:10.3390/cells10102596 · Cited by 21
The Yeast Hsp70 Cochaperone Ydj1 Regulates Functional Distinction of Ssa Hsp70s in the Hsp90 Chaperoning Pathway
Gaur, D., Singh, P. R., Guleria, J., Gupta, A., Kaur, S., & Sharma, D. (2020) · Genetics · doi:10.1534/genetics.120.303190 · Cited by 16
Prediction of dual agents as an activator of mutant p53 and inhibitor of Hsp90 by docking, molecular dynamic simulation and virtual screening
Abbasi, M., Sadeghi‐Aliabadi, H., Hassanzadeh, F., & Amanlou, M. (2015) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2015.08.001 · Cited by 18
“The function of the Hsp90 dimer is affiliated to its binding apability and hydrolysis of ATP [4].”
BackgroundInfluential
Chaperone Proteins Select and Maintain [PIN+] Prion Conformations in Saccharomyces cerevisiae
Lancaster, D. L., Dobson, C. M., & Rachubinski, R. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.377564 · Cited by 16
Evidence for Hsp90 Co-chaperones in Regulating Hsp90 Function and Promoting Client Protein Folding
Cox, M. B., & Johnson, J. L. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7477-1_28 · Cited by 21
Nematode Sgt1-Homologue D1054.3 Binds Open and Closed Conformations of Hsp90 via Distinct Binding Sites
Eckl, J. M., Drazic, A., Rutz, D. A., & Richter, K. (2014) · Biochemistry · doi:10.1021/bi5000542 · Cited by 12
Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation
Echeverría, P. C., Forafonov, F., Pandey, D. P., Mühlebach, G., & Picard, D. (2011) · BioData Mining · doi:10.1186/1756-0381-4-15 · Cited by 16
“These co-chaperones assist Hsp90 by modulating its ATPase cycle and by facilitating its interactions with various client/substrate proteins [8-10].”
Background
The evolution and diversification of the Hsp90 co-chaperone system
Engler, S., & Büchner, J. (2025) · Biological Chemistry · doi:10.1515/hsz-2025-0112 · Cited by 12
Characterization of an Hsp90-Independent Interaction between Co-Chaperone p23 and Transcription Factor p53
Wu, H., Hyun, J.-S., Martinez‐Yamout, M. A., Park, S. J., & Dyson, H. J. (2018) · Biochemistry · doi:10.1021/acs.biochem.7b01076 · Cited by 15
“Nature of the Interaction between p53(88-312) and p23(1-160)”
BackgroundMethodResultInfluential
Detecting Posttranslational Modifications of Hsp90
Sager, R., Woodford, M. R., Neckers, L., & Mollapour, M. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7477-1_16 · Cited by 14
Comparative studies of the low-resolution structure of two p23 co-chaperones for Hsp90 identified in Plasmodium falciparum genome
da Silva, N. S. M., Seraphim, T. V., Minari, K., Barbosa, L. R. S., & Borges, J. C. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.11.161 · Cited by 16
Expression of five AtHsp90 genes in Saccharomyces cerevisiae reveals functional differences of AtHsp90s under abiotic stresses.
Song, H., Fan, P., Shi, W.-L., Zhao, R.-M., & Li, Y.-X. (2010) · Journal of plant physiology · doi:10.1016/j.jplph.2010.03.016 · Cited by 13
Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants
Kröber-Boncardo, C., Lorenzen, S., Brinker, C., & Clos, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-72724-x · Cited by 12
Hsp90 sensitivity to ADP reveals hidden regulation mechanisms
Halpin, J., & Street, T. O. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.08.005 · Cited by 11
“For example, the cochaperone Aha1 activates Hsp90 [3, 4], whereas Hop and p23 inhibit the ATPase [5, 6].”
Background
High Levels of Hsp90 Cochaperone p23 Promote Tumor Progression and Poor Prognosis in Breast Cancer by Increasing Lymph Node Metastases and Drug Resistance
Simpson, N. E., Lambert, W. M., Watkins, R. A., Giashuddin, S. M., Huang, S.-T. J., Oxelmark, E., Arju, R., Hochman, T., Goldberg, J. D., Schneider, R. J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1590 · Cited by 62
“p23 acts as a cochaperone, stabilizing the ATP-bound form of Hsp90, thereby stabilizing Hsp90 interactions with steroid receptors (SR) (3) and assisting Hsp90 in increasing the hormone binding affinities of many SRs (4-6).”
Defective glucocorticoid receptor signaling and keratinocyte-autonomous defects contribute to skin phenotype of mouse embryos lacking the Hsp90 co-chaperone p23
Madon-Simon, M., Grad, I., Bayo, P., Pérez, P., & Picard, D. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180035 · Cited by 10
“Apart from being an important regulator of the Hsp90 chaperoning cycle [9,8], p23 has its own Hsp90-independent chaperone activity, which can prevent protein aggregation and maintain proteins in a folding-competent state [10–12].”
Background
Hsp90 oligomerization process: How can p23 drive the chaperone machineries?
Lepvrier, E., Nigen, M., Moullintraffort, L., Chat, S., Allegro, D., Barbier, P., Thomas, D., Nazabal, A., & Garnier, C. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2015.07.003 · Cited by 9
Synchrotron radiation studies of non-crystalline systems
Koch, M. H. J., & Bras, W. (2008) · Annual Reports Section C (Physical Chemistry) · doi:10.1039/b703892p · Cited by 11
Hsp90 Co-chaperones as Drug Targets in Cancer: Current Perspectives
Edkins, A. L. (2016) · Topics in medicinal chemistry · doi:10.1007/7355_2015_99 · Cited by 14
In silico analysis of the HSP90 chaperone system from the African trypanosome, Trypanosoma brucei
Jamabo, M., Bentley, S. J., Macucule-Tinga, P., Tembo, P., Edkins, A. L., & Boshoff, A. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.947078 · Cited by 8
“1 p23 The co-chaperone p23 is a small acidic protein that binds the HSP90 NBD to stabilize the closed conformation of HSP90, inhibiting ATPase activity and preventing client protein release from the complex (Young, 2000; McLaughlin et al., 2006).”
Background
Characterization of Hsp90 Co-Chaperone p23 Cleavage by Caspase-7 Uncovers a Peptidase–Substrate Interaction Involving Intrinsically Disordered Regions
Martini, C., Bédard, M., Lavigne, P., & Denault, J. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00298 · Cited by 10
Computational Modeling of the Hsp90 Interactions with Cochaperones and Small-Molecule Inhibitors
Verkhivker, G. M. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7477-1_19 · Cited by 10
“Tuning” the ATPase Activity of Hsp90
Prodromou, C., & Morgan, R. M. L. (2015) · Springer eBooks · doi:10.1007/978-3-319-24780-9_23 · Cited by 7
Detecting HSP90 Phosphorylation
Mollapour, M., & Neckers, L. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-295-3_5 · Cited by 9
Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer
Backe, S. J., Sager, R., Meluni, K. A., Woodford, M. R., Bourboulia, D., & Mollapour, M. (2022) · Biomolecules · doi:10.3390/biom12070928 · Cited by 9
Monitoring the Conformation of the Sba1/Hsp90 Complex in the Presence of Nucleotides with Mn(II)-Based Double Electron–Electron Resonance
Giannoulis, A., Feintuch, A., Unger, T., Amir, S., & Goldfarb, D. (2021) · Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.1c03641 · Cited by 8
Differential Proteomic Analysis of Human Erythroblasts Undergoing Apoptosis Induced by Epo-Withdrawal
Pellegrin, S., Heesom, K., Satchwell, T., Hawley, B. R., Daniels, G., van den Akker, E., & Toye, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038356 · Cited by 8
Hsp90 and associates shaping parasite biology
Gahlawat, A., Bhattacharyya, S., & Bhattacharyya, M. (2025) · Msphere · doi:10.1128/msphere.00329-25 · Cited by 7
“By slowing ATPase activity, p23 retains Hsp90 in an ATP-bound state, prolonging client protein interaction for activation (65).”
Allosteric Mechanism of the Hsp90 Chaperone Interactions with Cochaperones and Client Proteins by Modulating Communication Spines of Coupled Regulatory Switches: Integrative Atomistic Modeling of Hsp90 Signaling in Dynamic Interaction Networks
Astl, L., Stetz, G., & Verkhivker, G. M. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00380 · Cited by 8
HSP-90/kinase complexes are stabilized by the large PPIase FKB-6
Sima, S., Barkovits, K., Marcus, K., Schmauder, L., Hacker, S. M., Hellwig, N., Morgner, N., & Richter, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-91667-5 · Cited by 5
A chemical crosslinking method for the analysis of binding partners of heat shock protein-90 in intact cells
Song, S., Kole, S., & Bernier, M. (2012) · BioTechniques · doi:10.2144/000113856 · Cited by 5
“Consistent with this notion is the fact that protein-protein interactions of Hsp90 and its co-chaperones are refractory to either the pharmacological inhibition of Hsp90 ATPase function or expression of Hsp90 mutants lacking the C-terminal homodimerization domain (27,28).”
Background
Mass spectrometric analysis of intact macromolecular chaperone complexes.
van Duijn, E., & Heck, A. (2006) · Drug Discovery Today : Technologies · doi:10.1016/j.ddtec.2006.03.008 · Cited by 5
Hsp90 Quaternary Structures and the Chaperone Cycle: Highly Flexible Dimeric and Oligomeric Structures and Their Regulation by Co-Chaperones
Lepvrier, E., Thomas, D., & Garnier, C. (2018) · Current Protoemics · doi:10.2174/1570164615666180522095147 · Cited by 4
Progress in Molecular Chaperone Regulation of Heat Shock Protein 90 and Cancer
Rui, Z., Xiao-Yun, G., Xing-Chuang, X., Jiang, Y., Huang, Z., & Xiang, F. (2018) · Chinese Journal of Analytical Chemistry · doi:10.1016/s1872-2040(17)61071-5 · Cited by 4
Re-examining HSPC1 inhibitors
Lee, S. L., Dempsey‐Hibbert, N., Vimalachandran, D., Wardle, T. D., Sutton, P. A., & Williams, J. H. H. (2017) · Cell Stress and Chaperones · doi:10.1007/s12192-017-0774-0 · Cited by 6
“These results confirm that the function of HSPC1 inhibitor is mediated through its ability to degrade client proteins and support the findings published in the literature (McLaughlin et al. 2006; Okui et al. 2011; Lee et al. 2011).”
Hsp90: A means to an end
Whalen, K. M., & Freeman, B. (2026) · Cell Stress and Chaperones · doi:10.1016/j.cstres.2026.100190 · Cited by 3
Identification of the Chenopodium quinoa HSP90 Gene Family and Functional Analysis of CqHSP90.1c and CqHSP90.6a Under High-Temperature Stress in Transgenic Arabidopsis thaliana
Chen, F., Wang, W., Liu, W., Song, J., Chen, S., An, Y., Yin, H., & Guo, S. (2025) · Plants · doi:10.3390/plants14172770 · Cited by 3
“As a co-chaperone of HSP90, P23 stabilizes the conformational state of HSP90 through inhibiting ATP hydrolysis [46].”
Identification of heat shock-inducible transcripts and Hop (Hsp-organizing protein)-interacting proteins in orchardgrass (Dactylis glomerata L.)
Cha, J., Baek, D., Lee, K.-W., Cheong, M., Hong, S., & Son, D. (2018) · Acta Physiologiae Plantarum · doi:10.1007/s11738-018-2708-6 · Cited by 3
Computational Studies of Allosteric Regulation in the Hsp90 Molecular Chaperone: From Functional Dynamics and Protein Structure Networks to Allosteric Communications and Targeted Anti‐Cancer Modulators
Verkhivker, G. M. (2014) · Israel Journal of Chemistry · doi:10.1002/ijch.201300143 · Cited by 4
Crystal structure and functional analysis identify the P‐loop containing protein YFH7 of Saccharomyces cerevisiae as an ATP‐dependent kinase
Gueguen-Chaignon, V., Chaptal, V., Larivière, L., Costa, N., Lopes, P., Moréra, S., & Nessler, S. (2008) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.21740 · Cited by 3
Functional Characterization of Cassava A20/AN1 Genes (Metip4, Metip8, and Metip11) in Multiple Abiotic Stresses
Chen, Y.-L., Huang, C., Wu, Y., Fan, X.-W., & Li, Y.-Z. (2025) · Food and Energy Security · doi:10.1002/fes3.70114 · Cited by 2
4.2 – Amino Acids, Peptides and Proteins
Schermann, J. (2008) · Elsevier eBooks · doi:10.1016/b978-044452708-0.50006-x · Cited by 2
FRET Assays for the Identification of C. albicans HSP90-Sba1 and Human HSP90α-p23 Binding Inhibitors
Kohlmann, P., Krylov, S. N., Marchand, P., & Jose, J. (2024) · Pharmaceuticals · doi:10.3390/ph17040516 · Cited by 1
“For AMP-PNP binding to human HSP90 β at 25 For the human HSP90 β –p23 complex, a K d value of 39 ± 12 µ M of AMP-PNP binding is reported [34].”
BackgroundMethodResultInfluential
Decrypting the languages of allostery in membrane-bound K-Ras4B using four complementary in silico approachesPreprint
Castelli, M., Marchetti, F., Osuna, S., Oliveira, A. S., Mulholland, A., Serapian, S. A., & Colombo, G. (2023) · bioRxiv · doi:10.1101/2023.07.14.549022 · Cited by 1
Functional Protein Interactions in Steroid Receptor-Chaperone Complexes
Ratajczak, T., Rudi, K., Cluning, C., & Bryan, K. R. (2012) · InTech eBooks · doi:10.5772/38339 · Cited by 1
“p23 is an essential component involved in stabilizing mature steroid receptor-Hsp90 complexes and binds to the ATP-bound conformation of a Hsp90 dimer characterised by high affinity for client proteins (Ali et al. , 2006; Felts & Toft, 2003; McLaughlin et al. , 2006; Richter et al. , 2004).”
Background
Emergence and Characterization of the p23 Molecular Chaperone
Echtenkamp, F., & Freeman, B. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1130-1_9 · Cited by 1
“state [40, 44].”
Structural analysis of de novo-designed binders targeting the closed state of HSP90
Srivastava, D., Singh, S., Boyd, K. K., & Artemyev, N. O. (2026) · Structure · doi:10.1016/j.str.2026.09.007
Structural analysis of de novo designed binders targeting the closed state of HSP90Preprint
Srivastava, D., Singh, S., Boyd, K. K., & Artemyev, N. (2026) · bioRxiv · doi:10.64898/2026.06.03.729966
“These drugs bind Co-chaperone p23 preferentially binds and stabilizes closed HSP90 thereby extending client folding window and promoting maturation [20, 26, 28]. p23 is upregulated in multiple cancers and facilitates stabilization of oncogenic HSP90 clients [8, 11, 29, 30].”
Evolution of Hsp90 targeting: From stress biology to clinical translation
Zarguan, I., Belayachi, L., Benjouad, A., & Chadli, A. (2026) · Cell Stress and Chaperones · doi:10.1016/j.cstres.2026.100193
A new FKBP51-GR-p23-Hsp902 multi-cochaperone complex identified and characterized by site-specific in-cell photocrosslinkingPreprint
Taubert, M. C., Kühn, A., Baischew, A., Käseberg, Y., Betschinske, J., & Hausch, F. (2025) · bioRxiv · doi:10.1101/2025.06.09.658717
“This would keep the GR tethered to Hsp90, thereby prolonging the time for correct folding of the GR [6].”
The Hsp90 chaperone system from the African trypanosome, Trypanosoma bruceiPreprint
Jamabo, M., Bentley, S. J., Macucule-Tinga, P., Edkins, A. L., & Boshoff, A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.15.435448
Identification of cytosolic factors interacting with mitochondrial preproteins
Hoseini, H. (2016) · doi:10.15496/publikation-8945
“Other co-chaperones such as p23/Sba1 inhibit the Hsp90 ATPase activity by binding preferentially to its N-terminal domain in the closed, nucleotide-bound state (Ali et al., 2006, McLaughlin et al., 2006).”
Background
Investigating Evolutionary Innovation in Yeast Heat Shock Protein 90
Cote-Hammarlof, P. A. (2020) · doi:10.13028/tns2-1515
“…conformational changes that allow Hsp90 to bind to partially folded clients, stabilizing specific folding intermediates that in turn allows clients to attain their full function (Figure 1.2) (Leach et al. 2012) (Lotz et al. 2003; Roe et al. 2004; McLaughlin et al. 2006; 36 Onuoha et al. 2008).”
BackgroundInfluential
Regulation of protein homeostasis in acute and chronic stress
Wu, D. (2019) · doi:10.33612/diss.96277662
“The ATP-dependent Hsp90 machines, regulated by a multitude of co-factors (50, 51), and”
Background
Systematic Experimental Determination of Functional Constraints on Proteins and Adaptive Potential of Mutations: A Dissertation
Li, J. (2016) · doi:10.13028/m25c74
“In the ATP cycle, multiple co-chaperones individually or collectively affect functions of Hsp90 by organizing interactions between Hsp90 and other chaperones (HOP) [115], activating (Aha1) or inhibiting (Cdc37 and p23) ATP hydrolysis [116-118], and recruiting clients (Cdc37) [119].”
Background
Analysis of Regulatory Mechanisms on RNA Interference by Molecular Chaperone Hsp90 and Protein Phosphorylation in Yeast
Wang, Y. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3zw19121
A Hsp90 és az adipogenezis kapcsolatának vizsgálata
Nguyễn, M. T. (2014) · Semmelweis University Repository (Semmelweis University) · doi:10.14753/se.2014.1971
“A p23 a kliens fehérjét úgy ejti csapdába, hogy csökkenti a Hsp90 konformációs hajlékonyságát, ami stimulálja az ATP-kötést és ezzel egy időben gátolja az ATPáz aktivitást (49).”
Analysis of the Conformational Dynamics of Hsp70 and Hsp90 Chaperones
Graf, C. (2008) · doi:10.11588/heidok.00008696
“18 cycle to trap client proteins (McLaughlin et al., 2006; Richter et al., 2004; Siligardi et al., 2002), while the partner protein Aha1 strongly stimulates the ATPase activity (Panaretou et al.”
Targeting Hsp90 Function to Treat Cancer: Much More to Be Learned
Whitesell, L. J., & McLellan, C. A. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6401-2_13
“An absolute requirement for cooperation between the ATPase activities of each monomer during the chaperoning of clients by human Hsp90, however, has been questioned (McLaughlin et al., 2006).”
Background

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: McLaughlin, Stephen H.
Sobott, Frank
Yao, Zhong-ping
Zhang, Wei
Laue, Ernest D.
Robinson, Carol V.
Jackson, Sophie E.
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Metadata

Record

About these checks