Conformational equilibria in allosteric control of Hsp70 chaperones

Wang, Wei; Liu, Qinglian; Liu, Qun; Hendrickson, Wayne A.

doi:10.1016/j.molcel.2021.07.039

Title: Conformational equilibria in allosteric control of Hsp70 chaperones

Journal Article · Fri Oct 01 00:00:00 EDT 2021 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2021.07.039· OSTI ID:1891365

Wang, Wei; Liu, Qinglian; Liu, Qun; Hendrickson, Wayne A.

Heat-shock proteins of 70 kDa (Hsp70s) are vital for all of life, notably important in protein folding. Hsp70s use ATP binding and hydrolysis at a nucleotide-binding domain (NBD) to control the binding and release of client polypeptides at a substrate-binding domain (SBD); however, the mechanistic basis for this allostery has been elusive. Here, we first characterize biochemical properties of selected domain-interface mutants in bacterial Hsp70 DnaK. We then develop a theoretical model for allosteric equilibria among Hsp70 conformational states to explain the observations: a restraining state, Hsp70_R-ATP, restricts ATP hydrolysis and binds peptides poorly; whereas a stimulating state, Hsp70_S-ATP, hydrolyzes ATP rapidly and has high intrinsic substrate affinity but rapid binding kinetics. Finally, we support this model for allosteric regulation with DnaK structures obtained in the postulated stimulating state S, with biochemical tests of the S-state interface, and with improved peptide-binding-site definition in an R-state structure.

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Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); American Heart Association; Virginia Commonwealth University

Grant/Contract Number:: P30 GM124165; P41 GM103403; SC0012704; R01GM107462; R01GM098592; R21AI140006; 17GRNT33660506

OSTI ID:: 1891365

Alternate ID(s):: OSTI ID: 1822850; OSTI ID: 1868837

Report Number(s):: BNL-222181-2021-JAAM; S1097276521006237; PII: S1097276521006237

Journal Information:: Molecular Cell, Journal Name: Molecular Cell Vol. 81 Journal Issue: 19; ISSN 1097-2765

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (66)

Clustal Omega for making accurate alignments of many protein sequences: Clustal Omega for Many Protein Sequences Sievers, Fabian; Higgins, Desmond G. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3290	journal	October 2017
Allostery and cooperativity revisited Cui, Qiang; Karplus, Martin Protein Science, Vol. 17, Issue 8 https://doi.org/10.1110/ps.03259908	journal	August 2008
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
Kinetics of the conformational cycle of Hsp70 reveals the importance of the dynamic and heterogeneous nature of Hsp70 for its function Wu, Si; Hong, Liu; Wang, Yuqing Proceedings of the National Academy of Sciences, Vol. 117, Issue 14 https://doi.org/10.1073/pnas.1914376117	journal	March 2020
Pathways of allosteric regulation in Hsp70 chaperones Kityk, Roman; Vogel, Markus; Schlecht, Rainer Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms9308	journal	September 2015
Insights into the molecular mechanism of allostery in Hsp70s Mayer, Matthias P.; Kityk, Roman Frontiers in Molecular Biosciences, Vol. 2 https://doi.org/10.3389/fmolb.2015.00058	journal	October 2015
Molecular Chaperone Functions in Protein Folding and Proteostasis Kim, Yujin E.; Hipp, Mark S.; Bracher, Andreas Annual Review of Biochemistry, Vol. 82, Issue 1 https://doi.org/10.1146/annurev-biochem-060208-092442	journal	June 2013
The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions Daugaard, Mads; Rohde, Mikkel; Jäättelä, Marja FEBS Letters, Vol. 581, Issue 19 https://doi.org/10.1016/j.febslet.2007.05.039	journal	May 2007
Allosteric Regulation of Hsp70 Chaperones Involves a Conserved Interdomain Linker Vogel, Markus; Mayer, Matthias P.; Bukau, Bernd Journal of Biological Chemistry, Vol. 281, Issue 50 https://doi.org/10.1074/jbc.M609020200	journal	October 2006
Bacterial Hsp70 resolves misfolded states and accelerates productive folding of a multi-domain protein Imamoglu, Rahmi; Balchin, David; Hayer-Hartl, Manajit Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-14245-4	journal	January 2020
Recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones Mayer, Matthias P.; Gierasch, Lila M. Journal of Biological Chemistry, Vol. 294, Issue 6 https://doi.org/10.1074/jbc.REV118.002810	journal	February 2019
Structural and Energetic Basis of Allostery Hilser, Vincent J.; Wrabl, James O.; Motlagh, Hesam N. Annual Review of Biophysics, Vol. 41, Issue 1 https://doi.org/10.1146/annurev-biophys-050511-102319	journal	June 2012
Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix Liebschner, Dorothee; Afonine, Pavel V.; Baker, Matthew L. Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 10 https://doi.org/10.1107/S2059798319011471	journal	October 2019
Mitochondrial Hsp70 Ssc1: Role in Protein Folding Liu, Qinglian; Krzewska, Joanna; Liberek, Krzysztof Journal of Biological Chemistry, Vol. 276, Issue 9 https://doi.org/10.1074/jbc.M009519200	journal	March 2001
Structural Basis for the Cooperation of Hsp70 and Hsp110 Chaperones in Protein Folding Polier, Sigrun; Dragovic, Zdravko; Hartl, F. Ulrich Cell, Vol. 133, Issue 6 https://doi.org/10.1016/j.cell.2008.05.022	journal	June 2008
Determining the Dimensions of the Drug-binding Domain of Human P-glycoprotein Using Thiol Cross-linking Compounds as Molecular Rulers Loo, Tip W.; Clarke, David M. Journal of Biological Chemistry, Vol. 276, Issue 40 https://doi.org/10.1074/jbc.C100467200	journal	October 2001
The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase Sharma, Sandeep K.; De Los Rios, Paolo; Christen, Philipp Nature Chemical Biology, Vol. 6, Issue 12 https://doi.org/10.1038/nchembio.455	journal	October 2010
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Peptide binding and release by proteins implicated as catalysts of protein assembly Flynn, G.; Chappell, T.; Rothman, J. Science, Vol. 245, Issue 4916 https://doi.org/10.1126/science.2756425	journal	July 1989
The Second Step of ATP Binding to DnaK Induces Peptide Release Theyssen, Holger; Schuster, Hans-Peter; Packschies, Lars Journal of Molecular Biology, Vol. 263, Issue 5 https://doi.org/10.1006/jmbi.1996.0606	journal	November 1996
Structural basis of the 70-kilodalton heat shock cognate protein ATP hydrolytic activity. I. Kinetic analyses of active site mutants. Wilbanks, S. M.; DeLuca-Flaherty, C.; McKay, D. B. Journal of Biological Chemistry, Vol. 269, Issue 17 https://doi.org/10.1016/S0021-9258(18)99960-6	journal	April 1994
Large-Scale Conformational Transitions and Dimerization Are Encoded in the Amino-Acid Sequences of Hsp70 Chaperones Malinverni, Duccio; Marsili, Simone; Barducci, Alessandro PLOS Computational Biology, Vol. 11, Issue 6 https://doi.org/10.1371/journal.pcbi.1004262	journal	June 2015
Three-dimensional structure of the ATPase fragment of a 70K heat-shock cognate protein Flaherty, Kevin M.; DeLuca-Flaherty, Camilla; McKay, David B. Nature, Vol. 346, Issue 6285 https://doi.org/10.1038/346623a0	journal	August 1990
Insights into Hsp70 Chaperone Activity from a Crystal Structure of the Yeast Hsp110 Sse1 Liu, Qinglian; Hendrickson, Wayne A. Cell, Vol. 131, Issue 1 https://doi.org/10.1016/j.cell.2007.08.039	journal	October 2007
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
DnaK, hsp73, and their molten globules. Two different ways heat shock proteins respond to heat. Palleros, D. R.; Reid, K. L.; McCarty, J. S. Journal of Biological Chemistry, Vol. 267, Issue 8 https://doi.org/10.1016/S0021-9258(18)42763-9	journal	March 1992
The Hsp70 chaperone network Rosenzweig, Rina; Nillegoda, Nadinath B.; Mayer, Matthias P. Nature Reviews Molecular Cell Biology, Vol. 20, Issue 11 https://doi.org/10.1038/s41580-019-0133-3	journal	June 2019
Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones Zhuravleva, A.; Gierasch, L. M. Proceedings of the National Academy of Sciences, Vol. 108, Issue 17 https://doi.org/10.1073/pnas.1014448108	journal	April 2011
A Functional DnaK Dimer Is Essential for the Efficient Interaction with Hsp40 Heat Shock Protein Sarbeng, Evans Boateng; Liu, Qingdai; Tian, Xueli Journal of Biological Chemistry, Vol. 290, Issue 14 https://doi.org/10.1074/jbc.M114.596288	journal	April 2015
An Interdomain Energetic Tug-of-War Creates the Allosterically Active State in Hsp70 Molecular Chaperones Zhuravleva, Anastasia; Clerico, Eugenia M.; Gierasch, Lila M. Cell, Vol. 151, Issue 6 https://doi.org/10.1016/j.cell.2012.11.002	journal	December 2012
Principles that Govern the Folding of Protein Chains Anfinsen, C. B. Science, Vol. 181, Issue 4096 https://doi.org/10.1126/science.181.4096.223	journal	July 1973
Mutations in the C-terminal fragment of DnaK affecting peptide binding. Burkholder, W. F.; Zhao, X.; Zhu, X. Proceedings of the National Academy of Sciences, Vol. 93, Issue 20 https://doi.org/10.1073/pnas.93.20.10632	journal	October 1996
Transformations to optimize the superposition of similar structures Hendrickson, W. A. Acta Crystallographica Section A, Vol. 35, Issue 1 https://doi.org/10.1107/S0567739479000279	journal	January 1979
Structure of the Hsp110:Hsc70 Nucleotide Exchange Machine Schuermann, Jonathan P.; Jiang, Jianwen; Cuellar, Jorge Molecular Cell, Vol. 31, Issue 2 https://doi.org/10.1016/j.molcel.2008.05.006	journal	July 2008
Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP Qi, Ruifeng; Sarbeng, Evans Boateng; Liu, Qun Nature Structural & Molecular Biology, Vol. 20, Issue 7 https://doi.org/10.1038/nsmb.2583	journal	May 2013
Theory of Allosteric Regulation in Hsp70 Molecular Chaperones Hendrickson, Wayne A. QRB Discovery, Vol. 1 https://doi.org/10.1017/qrd.2020.10	journal	January 2020
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Crystal Structure of the Nucleotide Exchange Factor GrpE Bound to the ATPase Domain of the Molecular Chaperone DnaK Harrison, Celia J.; Hayer-Hartl, Manajit; Liberto, Maurizio Di Science, Vol. 276, Issue 5311 https://doi.org/10.1126/science.276.5311.431	journal	April 1997
Comparison of Experimental Binding Data and Theoretical Models in Proteins Containing Subunits ^* Koshland, D. E.; Némethy, G.; Filmer, D. Biochemistry, Vol. 5, Issue 1 https://doi.org/10.1021/bi00865a047	journal	January 1966
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Kinetics of molecular chaperone action Schmid, D.; Baici, A.; Gehring, H. Science, Vol. 263, Issue 5149 https://doi.org/10.1126/science.8310296	journal	February 1994
Loops in Proteins Can Be Modeled as Worm-Like Chains Zhou, Huan-Xiang The Journal of Physical Chemistry B, Vol. 105, Issue 29 https://doi.org/10.1021/jp011355n	journal	July 2001
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Intragenic suppressors of Hsp70 mutants: Interplay between the ATPase- and peptide-binding domains Davis, J. E.; Voisine, C.; Craig, E. A. Proceedings of the National Academy of Sciences, Vol. 96, Issue 16 https://doi.org/10.1073/pnas.96.16.9269	journal	August 1999
Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate Bertelsen, E. B.; Chang, L.; Gestwicki, J. E. Proceedings of the National Academy of Sciences, Vol. 106, Issue 21 https://doi.org/10.1073/pnas.0903503106	journal	May 2009
Key features of an Hsp70 chaperone allosteric landscape revealed by ion-mobility native mass spectrometry and double electron-electron resonance Lai, Alex L.; Clerico, Eugenia M.; Blackburn, Mandy E. Journal of Biological Chemistry, Vol. 292, Issue 21 https://doi.org/10.1074/jbc.M116.770404	journal	May 2017
Hsp70 Chaperone Ligands Control Domain Association via an Allosteric Mechanism Mediated by the Interdomain Linker Swain, Joanna F.; Dinler, Gizem; Sivendran, Renuka Molecular Cell, Vol. 26, Issue 1 https://doi.org/10.1016/j.molcel.2007.02.020	journal	April 2007
Intermediates in allosteric equilibria of DnaK–ATP interactions with substrate peptides Wang, Wei; Hendrickson, Wayne A. Acta Crystallographica Section D Structural Biology, Vol. 77, Issue 5 https://doi.org/10.1107/S2059798321002436	journal	April 2021
Structural Dynamics of the DnaK–Peptide Complex Popp, Simone; Packschies, Lars; Radzwill, Nicole Journal of Molecular Biology, Vol. 347, Issue 5 https://doi.org/10.1016/j.jmb.2005.02.026	journal	April 2005
Structural Analysis of Substrate Binding by the Molecular Chaperone DnaK Zhu, X.; Zhao, X.; Burkholder, W. F. Science, Vol. 272, Issue 5268 https://doi.org/10.1126/science.272.5268.1606	journal	June 1996
Peptide-Induced Conformational Changes in the Molecular Chaperone DnaK Slepenkov, Sergey V.; Witt, Stephan N. Biochemistry, Vol. 37, Issue 47 https://doi.org/10.1021/bi981738k	journal	November 1998
Heat Shock Proteins Promote Cancer: It's a Protection Racket Calderwood, Stuart K.; Gong, Jianlin Trends in Biochemical Sciences, Vol. 41, Issue 4 https://doi.org/10.1016/j.tibs.2016.01.003	journal	April 2016
On the nature of allosteric transitions: A plausible model Monod, Jacque; Wyman, Jeffries; Changeux, Jean-Pierre Journal of Molecular Biology, Vol. 12, Issue 1 https://doi.org/10.1016/S0022-2836(65)80285-6	journal	May 1965
ATP-induced protein Hsp70 complex dissociation requires K+ but not ATP hydrolysis Palleros, Daniel R.; Raid, Katherine L.; Shi, Li Nature, Vol. 365, Issue 6447 https://doi.org/10.1038/365664a0	journal	October 1993
Nucleotide-induced Conformational Changes in the ATPase and Substrate Binding Domains of the DnaK Chaperone Provide Evidence for Interdomain Communication Buchberger, Alexander; Theyssen, Holger; Schröder, Hartwig Journal of Biological Chemistry, Vol. 270, Issue 28 https://doi.org/10.1074/jbc.270.28.16903	journal	July 1995
Structural Basis of Interdomain Communication in the Hsc70 Chaperone Jiang, Jianwen; Prasad, Kondury; Lafer, Eileen M. Molecular Cell, Vol. 20, Issue 4 https://doi.org/10.1016/j.molcel.2005.09.028	journal	November 2005
Protein Quality Control by Molecular Chaperones in Neurodegeneration Ciechanover, Aaron; Kwon, Yong Tae Frontiers in Neuroscience, Vol. 11 https://doi.org/10.3389/fnins.2017.00185	journal	April 2017
Structure and Dynamics of the ATP-Bound Open Conformation of Hsp70 Chaperones Kityk, Roman; Kopp, Jürgen; Sinning, Irmgard Molecular Cell, Vol. 48, Issue 6 https://doi.org/10.1016/j.molcel.2012.09.023	journal	December 2012
Symmetry, Rigidity, and Allosteric Signaling: From Monomeric Proteins to Molecular Machines Thirumalai, D.; Hyeon, Changbong; Zhuravlev, Pavel I. Chemical Reviews, Vol. 119, Issue 12 https://doi.org/10.1021/acs.chemrev.8b00760	journal	April 2019
The Role of ATP in the Functional Cycle of the DnaK Chaperone System McCarty, John S.; Buchberger, Alexander; Reinstein, Jochen Journal of Molecular Biology, Vol. 249, Issue 1 https://doi.org/10.1006/jmbi.1995.0284	journal	May 1995
Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 Morgner, Nina; Schmidt, Carla; Beilsten-Edmands, Victoria Cell Reports, Vol. 11, Issue 5 https://doi.org/10.1016/j.celrep.2015.03.063	journal	May 2015
Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins Schrank, T. P.; Bolen, D. W.; Hilser, V. J. Proceedings of the National Academy of Sciences, Vol. 106, Issue 40 https://doi.org/10.1073/pnas.0906510106	journal	September 2009
Kinetic Analysis of Interdomain Coupling in a Lidless Variant of the Molecular Chaperone DnaK: DnaK's Lid Inhibits Transition to the Low Affinity State Slepenkov, Sergey V.; Witt, Stephan N. Biochemistry, Vol. 41, Issue 40 https://doi.org/10.1021/bi0263208	journal	September 2002
Ulp1-SUMO Crystal Structure and Genetic Analysis Reveal Conserved Interactions and a Regulatory Element Essential for Cell Growth in Yeast Mossessova, Elena; Lima, Christopher D. Molecular Cell, Vol. 5, Issue 5 https://doi.org/10.1016/S1097-2765(00)80326-3	journal	May 2000
Exchange We Can Believe in Hendrickson, Wayne A.; Liu, Qinglian Structure, Vol. 16, Issue 8 https://doi.org/10.1016/j.str.2008.07.002	journal	August 2008
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007

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Title: Conformational equilibria in allosteric control of Hsp70 chaperones

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