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Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase
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Abstract
Holding kinases at the ready: About 60% of kinases only reach their active state in the presence of the molecular chaperone Hsp90 and its co-chaperone Cdc37. It is unclear how the chaperones facilitate kinase function or why only some kinases are chaperone-dependent. Verba et al. determined a 3.9 Å cryo–electron microscopy structure of Hsp90:Cdc37 in complex with the kinase Cdk4. Together, Hsp90 and Cdc37 trap the kinase in an open, partially unfolded state. Taking on this state probably has direct functional benefits. Science , this issue p. 1542
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“have been identified to contact the unfolded Cdk4 client in the Hsp90:Cdc37:Cdk4 closed state structure”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Verba et al., 2016
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“Cryo-EM structures of the client-bound Hsp90 reveal the client undergoes substantial unfolding, likely upon formation of the Hsp90 closed state”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Verba et al., 2016
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“in existing closed state structures (Huck et al., 2017; Verba et al., 2016) the CTD adopts this widened conformation in the absence of a bound H7e moiety, indicating this may result from NTD dimerization alone”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Verba et al., 2016
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“Both clients are threaded through the closed Hsp90 lumen, suggesting a universal binding mode for Hsp90 clients11,35”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [11]
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“we found that two hydrophobic residues may represent the common binding pattern of the Hsp90 client, which are I271 and I274 in AhR, L525 and L528 in GR,33 and V89 and V92 in Cdk428”
From Cryo-EM structure of the cytosolic AhR complex. (2023) · cites this paper as [28]
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“The N-lobe of Cdk4 is unfolded and threaded though the MD dimer cleft in the Hsp90:Cdc37:Cdk4 structure exposing a strand of residues that would be inaccessible in the folded state”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Verba et al., 2016
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“sharply contrasting with the unfolded kinase:Hsp90 structure11.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [11]
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“The kinase:Hsp90 structure11 first revealed how Hsp90 can stabilize an inactive client, but provided no insights to explain how Hsp90 can reactivate a client, such as GR.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [11]
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“The active, native GR in our complex starkly contrasts with the only other structure of a closed Hsp90:client complex, which stabilizes an unfolded kinase client11.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [11]
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“These findings support an emerging paradigm in which Hsp90 cochaperones make specific, direct contact with Hsp90 clients to aid in client recognition and function11,12.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [11]
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“20 mM sodium molybdate (used to stabilize the closed conformation of Hsp9011,42,43, likely by acting as a γ-phosphate analog to stabilize the post-ATP hydrolysis transition state of Hsp90 (Extended Data Fig. 2c))”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [11]
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“In the Hsp90:FKBP51:p23 structure FKBP51 extends from the CTD-TPR interaction along the Hsp90 MD, enabling the N-terminal FK1 domain to be positioned adjacent Hsp90 client interaction sites”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Verba et al., 2016
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“and by mediating client interaction [e.g., the kinase-specific Cdc37 (5, 6)].”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [6]
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Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Scalable molecular dynamics with NAMD
Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., & Schulten, K. (2005) · Journal of Computational Chemistry · doi:10.1002/jcc.20289 · Cited by 16,914
RELION: Implementation of a Bayesian approach to cryo-EM structure determination
Scheres, S. H. W. (2012) · Journal of Structural Biology · doi:10.1016/j.jsb.2012.09.006 · Cited by 5,446
CTFFIND4: Fast and accurate defocus estimation from electron micrographs
Rohou, A. L., & Grigorieff, N. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.08.008 · Cited by 4,759
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
Davis, I., Leaver‐Fay, A., Chen, V. B., Block, J. N., Kapral, G. J., Wang, X., Murray, L. W., Arendall, W. B., Snoeyink, J. S., Richardson, J. S., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm216 · Cited by 3,918
EMAN2: An extensible image processing suite for electron microscopy
Tang, G., Peng, L., Baldwin, P. R., Mann, D. S., Jiang, W., Rees, I., & Ludtke, S. J. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2006.05.009 · Cited by 2,914
Targeting cancer with small molecule kinase inhibitors
Zhang, J., Yang, P. L., & Gray, N. S. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2559 · Cited by 2,648
Rosenthal, P. B., & Henderson, R. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.07.013 · Cited by 2,416
Li, X.-M., Mooney, P., Zheng, S., Booth, C., Braunfeld, M. B., Gubbens, S., Agard, D., & Cheng, Y.-F. (2013) · Nature Methods · doi:10.1038/nmeth.2472 · Cited by 1,866
Self-citation
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Schopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540
Unravelling biological macromolecules with cryo-electron microscopy
Fernández-Leiro, R., & Scheres, S. H. W. (2016) · Nature · doi:10.1038/nature19948 · Cited by 420
Hsp90 and Hsp70 chaperones: Collaborators in protein remodeling
Genest, O., Wickner, S., & Doyle, S. M. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.rev118.002806 · Cited by 392
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Biebl, M. M., & Büchner, J. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034017 · Cited by 315
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Luengo, T. M., Mayer, M. P., & Rüdiger, S. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.10.004 · Cited by 282
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Wood, D. J., & Endicott, J. (2018) · Open Biology · doi:10.1098/rsob.180112 · Cited by 272
p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition
Guiley, K. Z., Stevenson, J. W., Lou, K., Barkovich, K. J., Kumarasamy, V. M., Wijeratne, T. U., Bunch, K. L., Tripathi, S. M., Knudsen, E. S., Witkiewicz, A. K., et al. (2019) · Science · doi:10.1126/science.aaw2106 · Cited by 231
Structure of Hsp90–Hsp70–Hop–GR reveals the Hsp90 client-loading mechanism
Wang, R. Y.-R., Noddings, C. M., Kirschke, E., Myasnikov, A. G., Johnson, J. L., & Agard, D. A. (2022) · Nature · doi:10.1038/s41586-021-04252-1 · Cited by 220
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Li, L., Wang, L., You, Q., & Xu, X. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00940 · Cited by 209
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Backe, S. J., Sager, R., Woodford, M. R., Makedon, A. M., & Mollapour, M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011833 · Cited by 208
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Chiosis, G., Digwal, C. S., Trepel, J. B., & Neckers, L. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00640-9 · Cited by 214
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Hume, S., Dianov, G. L., & Ramadan, K. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1002 · Cited by 207
Nebenfuehr, S., Kollmann, K., & Sexl, V. (2020) · International Journal of Cancer · doi:10.1002/ijc.33054 · Cited by 187
Wang, K., Shen, Y., Yang, Y. P., Gan, X., Liu, G., Hu, K., Li, Y., Gao, Z., Zhu, L., Yan, G., et al. (2019) · Nature Ecology & Evolution · doi:10.1038/s41559-019-0864-8 · Cited by 186
Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism
Noddings, C. M., Wang, R. Y.-R., Johnson, J. L., & Agard, D. A. (2022) · Nature · doi:10.1038/s41586-021-04236-1 · Cited by 164
Self-citationLang, B. J., Guerrero-Gimenez, M. E., Prince, T. L., Okusha, Y., Bonorino, C., & Calderwood, S. K. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03070-8 · Cited by 168
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Wang, H., Deng, G., Ai, M., Xu, Z., Mou, T., Yu, J., Liu, H., Wang, S., & Li, G. (2019) · Oncogene · doi:10.1038/s41388-018-0532-5 · Cited by 117
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Kravats, A. N., Hoskins, J. R., Reidy, M., Johnson, J. L., Doyle, S. M., Genest, O., Masison, D. C., & Wickner, S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1719969115 · Cited by 106
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Gestwicki, J. E., & Shao, H. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm118.002813 · Cited by 99
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Mader, S. L., López, A., Lawatscheck, J., Luo, Q., Rutz, D. A., Gámiz‐Hernández, A. P., Sattler, M., Büchner, J., & Kaila, V. R. I. (2020) · Nature Communications · doi:10.1038/s41467-020-15050-0 · Cited by 92
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Flynn, J. M., Rossouw, A., Cote-Hammarlof, P., Fragata, I., Mavor, D., Hollins, C., Bank, C., & Bolon, D. N. (2020) · eLife · doi:10.7554/elife.53810 · Cited by 91
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Naser, R., Aldehaiman, A., Díaz‐Galicia, E., & Arold, S. T. (2018) · Cancers · doi:10.3390/cancers10060196 · Cited by 90
Ferraro, M., D’Annessa, I., Moroni, E., Morra, G., Paladino, A., Rinaldi, S., Compostella, F., & Colombo, G. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00825 · Cited by 90
Woodford, M. R., Sager, R., Marris, E. T., Dunn, D. M., Blanden, A. R., Murphy, R. L., Rensing, N. R., Shapiro, O., Panaretou, B., Prodromou, C., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796700 · Cited by 89
Zuo, W., Pang, Q., Zhu, X., Yang, Q., Zhao, Q., He, G., Han, B., & Huang, W. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01601-1 · Cited by 108
Keramisanou, D., Aboalroub, A. A., Zhang, Z., Liu, W., Marshall, D., Diviney, A., Larsen, R. W., Landgraf, R., & Gelis, I. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.005 · Cited by 87
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Lee, K., Thwin, A. C., Nadel, C. M., Tse, E., Gates, S. N., Gestwicki, J. E., & Southworth, D. R. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.023 · Cited by 76
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Elnatan, D., Betegon, M., Liu, Y. X., Ramelot, T. A., Kennedy, M. A., & Agard, D. A. (2017) · eLife · doi:10.7554/elife.25235 · Cited by 78
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Wu, X., Yang, X., Xiong, Y., Li, R., Ito, T., Ahmed, T. A., Karoulia, Z., Adamopoulos, C., Wang, H., Wang, L., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00174-z · Cited by 75
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García‐Alonso, S., Mesa, P., Ovejero, L. D. L. P., Aizpurua, G., Lechuga, C. G., Zarzuela, E., Santiveri, C. M., Sanclemente, M., Muñoz, J., Musteanu, M., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.08.012 · Cited by 74
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Noddings, C. M., Johnson, J. L., & Agard, D. A. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01128-y · Cited by 75
“Our structures contribute to an emerging theme in which Hsp90 co-chaperones bind to distinct Hsp90 conformations, while simultaneously stabilizing specific client conformations to regulate client activity 12,13,41,42,54 .”
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Differential Regulation of G1 CDK Complexes by the Hsp90-Cdc37 Chaperone System
Hallett, S. T., Pastok, M. W., Morgan, R. M. L., Wittner, A., Blundell, K. L. I. M., Felletár, I., Wedge, S. R., Prodromou, C., Noble, M. E. M., Pearl, L. H., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.042 · Cited by 63
Ruan, Z., & Kannan, N. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803152115 · Cited by 59
Biebl, M. M., Lopez, A., Rehn, A., Freiburger, L., Lawatscheck, J., Blank, B., Sattler, M., & Buchner, J. (2021) · Nature Communications · doi:10.1038/s41467-021-21063-0 · Cited by 58
Hendershot, L. M., Buck, T. M., & Brodsky, J. L. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168418 · Cited by 65
Heider, M., Eichner, R., Stroh, J., Morath, V., Kuisl, A., Zecha, J., Lawatscheck, J., Baek, K., Garz, A.-K., Rudelius, M., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.046 · Cited by 60
Bickel, D., & Gohlke, H. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.115080 · Cited by 63
Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network
Lopez, A., Dahiya, V., Delhommel, F., Freiburger, L., Stehle, R., Asami, S., Rutz, D., Blair, L., Buchner, J., & Sattler, M. (2021) · Science Advances · doi:10.1126/sciadv.abl7295 · Cited by 59
Regulation of the Hsp90 system
Sima, S., & Richter, K. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.03.008 · Cited by 57
Multifaceted roles of HEAT SHOCK PROTEIN 90 molecular chaperones in plant development
Tichá, T., Samakovli, D., Kuchařová, A., Vavrdová, T., & Šamaj, J. (2020) · Journal of Experimental Botany · doi:10.1093/jxb/eraa177 · Cited by 60
Mechanistic basis for the recognition of a misfolded protein by the molecular chaperone Hsp90
Oroz, J., Kim, J. H., Chang, B. J., & Zweckstetter, M. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3380 · Cited by 58
Pan, T. S., Peng, Z., Tan, L., Zou, F., Zhou, N., Liu, B., Liang, L., Chen, C., Liu, J., Wu, L., et al. (2018) · Journal of Virology · doi:10.1128/jvi.01018-18 · Cited by 58
Hsp90 modulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways
Sun, P., Wang, Y., Gao, T. X., Li, K., Zheng, D., Liu, A., & Ni, Y. (2021) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-021-00723-2 · Cited by 56
Hsp multichaperone complex buffers pathologically modified Tau
Moll, A., Ramirez, L. M., Ninov, M., Schwarz, J., Urlaub, H., & Zweckstetter, M. (2022) · Nature Communications · doi:10.1038/s41467-022-31396-z · Cited by 60
The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions
Kolhe, J. A., Babu, N. L., & Freeman, B. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.021 · Cited by 59
Zhou, C. Y., Stoddard, C. I., Johnston, J. B., Trnka, M. J., Echeverria, I., Palovcak, E. J., Šali, A., Burlingame, A. L., Cheng, Y., & Narlikar, G. J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.029 · Cited by 56
Wolf, S., Amaral, M., Lowinski, M., Vallée, F., Müsil, D., Güldenhaupt, J., Dreyer, M. K., Bomke, J., Frech, M., Schlitter, J., et al. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.9b00592 · Cited by 53
Paladino, A., Woodford, M. R., Backe, S. J., Sager, R., Kancherla, P., Daneshvar, M., Chen, V. Z., Bourboulia, D., Ahanin, E. F., Prodromou, C., et al. (2020) · Chemistry - A European Journal · doi:10.1002/chem.202000615 · Cited by 56
Chaperone-Bound Clients: The Importance of Being Dynamic
Hiller, S. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.12.005 · Cited by 54
The interactions of molecular chaperones with client proteins: why are they so weak?
Arhar, T., Shkedi, A., Nadel, C. M., & Gestwicki, J. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101282 · Cited by 55
Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway
Oh, J., Hyun, J.-Y., & Varshavsky, A. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705898114 · Cited by 55
Alberti, G., Vergilio, G., Paladino, L., Barone, R., Cappello, F., de Macario, E. C., Macario, A. J. L., Bucchieri, F., & Rappa, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147792 · Cited by 57
Non-canonical roles of PFKFB3 in regulation of cell cycle through binding to CDK4
Jia, W., Zhao, X., Zhao, L., Yan, H., Li, J., Yang, H., Huang, G., & Liu, J. (2018) · Oncogene · doi:10.1038/s41388-017-0072-4 · Cited by 55
Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90
Sager, R., Woodford, M. R., Backe, S. J., Makedon, A. M., Baker-Williams, A. J., DiGregorio, B. T., Loiselle, D. R., Haystead, T., Zachara, N. E., Prodromou, C., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.018 · Cited by 54
Giannoulis, A., Feintuch, A., Barak, Y., Mazal, H., Albeck, S., Unger, T., Yang, F., Su, X., & Goldfarb, D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1916030116 · Cited by 54
Cryo-EM structure of the cytosolic AhR complex.
Wen, Z., Zhang, Y., Zhang, B., Hang, Y., Xu, L., Chen, Y., Xie, Q., Zhao, Q., Zhang, L., Li, G., et al. (2023) · Structure · doi:10.1016/j.str.2022.12.013 · Cited by 51
Controlling protein function by fine-tuning conformational flexibility
Schmid, S., & Hugel, T. (2020) · eLife · doi:10.7554/elife.57180 · Cited by 52
Dernovšek, J., & Tomašič, T. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108396 · Cited by 54
Bachman, A. B., Keramisanou, D., Xu, W., Beebe, K. E., Moses, M. A., Kumar, M. V. V., Gray, G., Noor, R. E., van der Vaart, A., Neckers, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02711-w · Cited by 50
Hsp90 provides a platform for kinase dephosphorylation by PP5
Jaime-Garza, M., Nowotny, C., Coutandin, D., Wang, F., Tabios, M. C., & Agard, D. A. (2023) · Nature Communications · doi:10.1038/s41467-023-37659-7 · Cited by 50
Self-citationWang, Z., Guo, L., Wang, Y., Zhou, H., Wang, S., Chen, D., Huang, J., & Xiong, K. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26294 · Cited by 50
Stetz, G., Tse, A., & Verkhivker, G. M. (2018) · Scientific Reports · doi:10.1038/s41598-018-25329-4 · Cited by 50
Methylation-regulated decommissioning of multimeric PP2A complexes
Wu, C.-G., Zheng, A., Jiang, L., Rowse, M., Stanevich, V., Chen, H., Li, Y., Satyshur, K. A., Johnson, B., Gu, T.-J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02405-3 · Cited by 45
Metadata
- Authors
- Verba, K. A., Wang, R. Y.-R., Arakawa, A., Liu, Y., Shirouzu, M., Yokoyama, S., & Agard, D. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- RIKEN (JP)
- Corresponding author
- Agard, David A.
- ORCID
- Venue
- Science
- Published
- 2016-06-24
- Volume
- 352
- Issue
- 6293
- Pages
- 1542-1547
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5373496
- OpenAlex
- W2467034934
- Semantic Scholar
- be9d874235bbeead8cd0fdf0f8296dc124cc3bd3
- Cited by
- 424
- References
- 58
- Citations by year
- 2026: 25 · 2025: 23 · 2024: 35 · 2023: 44 · 2022: 53 · 2021: 52 · 2020: 52 · 2019: 52 · 2018: 40 · 2017: 39 · 2016: 7
- FWCI
- 23.90
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Protein Structure Initiative-Biology (U01 GM098254)
- American Association for Cancer Research-Breast Cancer Research Foundation (218084)
- HHMI Helen Hay Whitney Foundation Fellowship
- HHMI International Student Research Fellowship
- HHMI
- NIH National Institute of General Medical Sciences (P41 GM103310)
- NSF (ACI-1053575)
- 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, Cdc37, CDK4, kinase activation, molecular chaperones, protein complex structure
- MeSH terms
- Animals, Enzyme Stability, Humans, Models, Molecular, Protein Structure, Secondary, Cell Cycle Proteins, Chaperonins, HSP90 Heat-Shock Proteins, Multiprotein Complexes, Cyclin-Dependent Kinase 4, Protein Unfolding, Sf9 Cells
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