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UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor

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Title: UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor
Authors: Kopp, MC
Larburu, N
Vinoth, D
Adams, CJ
Ali, MMU
Item Type: Journal Article
Abstract: BiP is a major ER chaperone and suggested to act as primary sensor in the activation of the unfolded protein response (UPR). How BiP operates as a molecular chaperone and as an ER stress sensor is unknown. Here, by reconstituting components of human UPR, ER stress and BiP chaperone systems, we discover that the interaction of BiP with the luminal domains (LD) of UPR proteins, IRE1 and PERK, switch BiP from its chaperone cycle into an ER stress sensor cycle by preventing the binding of its cochaperones, with loss of ATPase stimulation. Furthermore, misfolded proteindependent dissociation of BiP from IRE1 is primed by ATP but not ADP. Our data elucidate a previously unidentified mechanistic cycle of BiP function that explains its ability to act as a Hsp70 chaperone and ER stress sensor.
Issue Date: 6-Nov-2019
Date of Acceptance: 1-Oct-2019
URI: http://hdl.handle.net/10044/1/74374
DOI: 10.1038/s41594-019-0324-9
ISSN: 1545-9985
Publisher: Nature Research
Start Page: 1053
End Page: 1062
Journal / Book Title: Nature Structural and Molecular Biology
Volume: 26
Copyright Statement: © 2019 Springer Nature Limited
Sponsor/Funder: Cancer Research UK
Cancer Research UK
Funder's Grant Number: 20752
23215
Keywords: 11 Medical and Health Sciences
03 Chemical Sciences
06 Biological Sciences
Biophysics
Developmental Biology
Publication Status: Published
Embargo Date: 2020-05-30
Appears in Collections:Faculty of Natural Sciences



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