Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone.

Abstract:

:Cytosolic HSP90 requires multiple cochaperones in folding client proteins. However, the function of gp96 (HSP90b1, grp94), an HSP90 paralogue in the endoplasmic reticulum (ER), is believed to be independent of cochaperones. Here, we demonstrate that gp96 chaperones multiple Toll-like receptors (TLRs), but not TLR3, in a manner that is dependent on another ER luminal protein, CNPY3. gp96 directly interacts with CNPY3, and the complex dissociates in the presence of adenosine triphosphate (ATP). Genetic disruption of gp96-CNPY3 interaction completely abolishes their TLR chaperone function. Moreover, we demonstrate that TLR9 forms a multimolecular complex with gp96 and CNPY3, and the binding of TLR9 to either molecule requires the presence of the other. We suggest that CNPY3 interacts with the ATP-sensitive conformation of gp96 to promote substrate loading. Our study has thus established CNPY3 as a TLR-specific cochaperone for gp96.

journal_name

Nat Commun

journal_title

Nature communications

authors

Liu B,Yang Y,Qiu Z,Staron M,Hong F,Li Y,Wu S,Li Y,Hao B,Bona R,Han D,Li Z

doi

10.1038/ncomms1070

subject

Has Abstract

pub_date

2010-09-21 00:00:00

pages

79

issn

2041-1723

pii

ncomms1070

journal_volume

1

pub_type

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