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.

Journal of Chemical Information and Modeling
Lindy AstlGennady M Verkhivker

Abstract

Conformational landscapes of the Hsp90 chaperones have revealed that the intrinsic plasticity and functional adaptability of these molecular chaperones to a large cohort of cochaperones and a vast protein clientele can be regulated by a number of single switch points broadly dispersed in the chaperone structure. A detailed dynamic view of the allosteric changes mediated by conformational switches and the mechanism of their coupling during the ATPase cycle remains poorly understood and presents an important area of investigation. In this work, we employed integrative computational modeling that included evolutionary and coevolutionary analyses, experiment-guided protein docking and structure modeling, molecular simulations, energetic analysis, and network modeling to perform a systematic characterization of molecular and network signatures of conformational switch points and dissect their allosteric cross-talk in the Hsp90 complexes with cochaperones and client proteins. Using a hierarchical modeling of dynamic interaction networks, we show that the allosteric regulation of the Hsp90 interactions with p23 and Aha1 cochaperones and p53 client protein may be determined by the intramolecular communication "spines" of spatially sepa...Continue Reading

References

Jul 27, 2001·Journal of Cellular Physiology·K Richter, J Buchner
Mar 1, 2002·Advances in Protein Chemistry·L H Pearl, C Prodromou
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·M Girvan, M E J Newman
Jun 25, 2002·Journal of Molecular Biology·Raphael GueroisLuis Serrano
Dec 12, 2002·Cellular and Molecular Life Sciences : CMLS·D Picard
Dec 31, 2002·Molecular Cell·Barry PanaretouChrisostomos Prodromou
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Dec 12, 2003·Bioinformatics·András Fiser, Andrej Sali
Mar 5, 2004·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·M E J Newman, M Girvan
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Jason C YoungF Ulrich Hartl
Jun 28, 2005·Nucleic Acids Research·Joost SchymkowitzLuis Serrano
Sep 10, 2005·Biophysical Journal·K V Brinda, Saraswathi Vishveshwara
Sep 15, 2005·Bioinformatics·L C MartinL M Wahl
Sep 22, 2005·Nature Reviews. Cancer·Luke Whitesell, Susan L Lindquist
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Dec 31, 2005·Nucleic Acids Research·Cathy H WuBaris Suzek
Jan 13, 2006·Journal of Molecular Biology·Stephen H McLaughlinSophie E Jackson
Mar 15, 2006·Biophysical Journal·Y DehouckM Rooman
Apr 21, 2006·Nature·Maruf M U AliLaurence H Pearl
May 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·M E J Newman
Jun 8, 2006·Annual Review of Biochemistry·Laurence H Pearl, Chrisostomos Prodromou
Jul 18, 2006·Nucleic Acids Research·Narcis Fernandez-FuentesAndrás Fiser
Aug 11, 2006·Bioinformatics·Aalt D J van Dijk, Alexandre M J J Bonvin
Oct 10, 2006·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·M E J Newman
Jan 16, 2007·Molecular Cell·Bradley T ScrogginsLen Neckers
Mar 1, 2007·Journal of the Royal Society, Interface·Andy Stirling
Mar 24, 2007·Bioinformatics·Baris E SuzekCathy H Wu
May 8, 2007·Journal of Molecular Biology·Nobuhiko TokurikiDan S Tawfik
Oct 3, 2007·The Journal of Biological Chemistry·Natalie Wayne, Daniel N Bolon
Feb 23, 2008·The Biochemical Journal·Laurence H PearlPaul Workman
May 22, 2008·The Journal of Biological Chemistry·Christian N CunninghamDavid A Agard
Oct 31, 2008·Nucleic Acids Research·Ofir GoldenbergNir Ben-Tal
Feb 24, 2009·Nature Structural & Molecular Biology·Martin HesslingJohannes Buchner
Feb 24, 2009·Nature Structural & Molecular Biology·Moritz MicklerThorsten Hugel
Apr 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anurag SethiZaida Luthey-Schulten
Jun 26, 2009·The Journal of Biological Chemistry·Otmar HainzlKlaus Richter
Aug 22, 2009·EMBO Reports·Marco RetzlaffJohannes Buchner
Feb 18, 2010·Molecular Cell·Marco RetzlaffJohannes Buchner

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