Next Article in Journal
Enhanced Hydrolysis of Cellulose in Ionic Liquid Using Mesoporous ZSM-5
Next Article in Special Issue
Probing Protein-Protein Interactions Using Asymmetric Labeling and Carbonyl-Carbon Selective Heteronuclear NMR Spectroscopy
Previous Article in Journal
MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(3), 528; https://doi.org/10.3390/molecules23030528

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

1
Department of Mathematical and Life Sciences, School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan
2
Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan
These authors contributed equally to this work.
Present address: Faculty of Pharma-Sciences, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
*
Author to whom correspondence should be addressed.
Received: 4 February 2018 / Revised: 18 February 2018 / Accepted: 24 February 2018 / Published: 27 February 2018
Full-Text   |   PDF [3568 KB, uploaded 27 February 2018]   |  

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 among residues within the Hsp70 SBD exist. View Full-Text
Keywords: Hsp70; SBD; αLid; NMR Hsp70; SBD; αLid; NMR
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Umehara, K.; Hoshikawa, M.; Tochio, N.; Tate, S.-I. Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication. Molecules 2018, 23, 528.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top