Wieteska, L, Shahidi, S and Zhuravleva, A orcid.org/0000-0001-6165-8509 (2017) Allosteric fine-tuning of the conformational equilibrium poises the chaperone BiP for post-translational regulation. eLife, 6. e29430.
Abstract
BiP is the only Hsp70 chaperone in the endoplasmic reticulum (ER) and similar to other Hsp70s, its activity relies on nucleotide- and substrate-controllable docking and undocking of its nucleotide-binding domain (NBD) and substrate-binding domain (SBD). However, little is known of specific features of the BiP conformational landscape that tune BiP to its unique tasks and the ER environment. We present methyl NMR analysis of the BiP chaperone cycle that reveals surprising conformational heterogeneity of ATP-bound BiP that distinguishes BiP from its bacterial homologue DnaK. This unusual poise enables gradual post-translational regulation of the BiP chaperone cycle and its chaperone activity by subtle local perturbations at SBD allosteric ‘hotspots’. In particular, BiP inactivation by AMPylation of its SBD does not disturb Hsp70 inter-domain allostery and preserves BiP structure. Instead it relies on a redistribution of the BiP conformational ensemble and stabilization the domain-docked conformation in presence of ADP and ATP.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, Wieteska et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Funding Information: | Funder Grant number BBSRC (Biotechnology & Biological Sciences Research Council) BB/M021874/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Sep 2017 09:20 |
Last Modified: | 13 Oct 2020 16:21 |
Status: | Published |
Publisher: | eLife Sciences Publications |
Identification Number: | 10.7554/eLife.29430 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:121088 |