Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Kohei UmeharaShin-Ichi Tate

Abstract

The stress-induced 70 kDa heat shock protein (Hsp70) functions as a molecular chaperone to maintain protein homeostasis. Hsp70 contains an N-terminal ATPase domain (NBD) and a C-terminal substrate-binding domain (SBD). The SBD is divided into the β subdomain containing the substrate-binding site (βSBD) and the α-helical subdomain (αLid) that covers the βSBD. In this report, the solution structures of two different forms of the SBD from human Hsp70 were solved. One structure shows the αLid bound to the substrate-binding site intramolecularly, whereas this intramolecular binding mode is absent in the other structure solved. Structural comparison of the two SBDs from Hsp70 revealed that client-peptide binding rearranges residues at the interdomain contact site, which impairs interdomain contact between the SBD and the NBD. Peptide binding also disrupted the inter-subdomain interaction connecting the αLid to the βSBD, which allows the binding of the αLid to the NBD. The results provide a mechanism for interdomain communication upon substrate binding from the SBD to the NBD via the lynchpin site in the βSBD of human Hsp70. In comparison to the bacterial ortholog, DnaK, some remarkable differences in the allosteric signal propagation...Continue Reading

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Mar 31, 2000·Nature Structural Biology·M PellecchiaE R Zuiderweg
Jul 6, 2000·Nature Structural Biology·M P MayerB Bukau
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
Dec 4, 2003·Journal of the American Chemical Society·W Bruce Turnbull, Antonio H Daranas
Jan 24, 2004·Current Biology : CB·Axel Mogk, Bernd Bukau
Nov 13, 2004·Cell Cycle·Mads Gyrd-HansenMarja Jäättelä
Mar 3, 2005·Genes & Development·Mikkel RohdeMarja Jäättelä
Mar 17, 2005·Cellular and Molecular Life Sciences : CMLS·M P Mayer, B Bukau
Nov 9, 2005·The Journal of Biological Chemistry·Joanna F SwainLila M Gierasch
Nov 26, 2005·Molecular Cell·Jianwen JiangRui Sousa
Jan 18, 2006·The Journal of Biological Chemistry·Vanesa Fernández-SáizArturo Muga
Feb 18, 2006·Trends in Biochemical Sciences·Stuart K CalderwoodDaniel R Ciocca
Apr 15, 2006·The Journal of Biological Chemistry·Wolfgang RistMatthias P Mayer
Jul 18, 2006·Current Topics in Medicinal Chemistry·Jeffrey L Brodsky, Gabriela Chiosis
Dec 23, 2006·Proteins·Aneerban BhattacharyaGaetano T Montelione
Oct 9, 2007·Analytical Biochemistry·Joel Tellinghuisen
Sep 23, 2008·European Biophysics Journal : EBJ·Peter Güntert
Oct 15, 2008·Journal of Molecular Endocrinology·Eirini MeimaridouJ Paul Chapple
May 15, 2009·Proceedings of the National Academy of Sciences of the United States of America·Eric B BertelsenErik R P Zuiderweg
Oct 13, 2009·Molecular Cell·J I-Ju LeuDonna L George
Oct 29, 2009·Current Topics in Medicinal Chemistry·Srikanth PaturyJason E Gestwicki
Feb 1, 2011·Nature Structural & Molecular Biology·Rainer SchlechtMatthias P Mayer
Nov 6, 2012·Molecular Cell·Roman KitykMatthias P Mayer
Apr 9, 2013·Carcinogenesis·Maureen E Murphy
May 28, 2013·Nature Structural & Molecular Biology·Ruifeng QiQinglian Liu
Sep 10, 2013·Trends in Biochemical Sciences·Matthias P Mayer
Dec 30, 2014·Chemistry & Biology·A Quamrul HassanHeather Sadlish
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Anastasia Zhuravleva, Lila M Gierasch
Sep 19, 2015·Nature Communications·Roman KitykMatthias P Mayer

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Citations

Nov 8, 2018·The Journal of Biological Chemistry·Olivier GenestShannon M Doyle
Mar 4, 2020·Cells·Zarema AlbakovaAlexander M Sapozhnikov
Aug 31, 2019·International Journal of Molecular Sciences·Alijah A Griffith, William Holmes
Aug 11, 2021·Annual Review of Microbiology·Sue WicknerOlivier Genest
Nov 20, 2020··Mohammad Kawsar Sharif SiamMohammad Umer Sharif Shohan

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Methods Mentioned

BETA
NMR
isothermal

Software Mentioned

TALOS
PROCHECK
- NMR
PSVS
XPLOR
MOLMOL
KUJIRA
NMRview
Microcal ORIGIN
NIH

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