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

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Citation

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

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

Nat Commun. 2010 Sep 21;1:79. doi: 10.1038/ncomms1070.

PubMed ID
20865800 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
EndoplasminP14625Details
Toll-like receptor 9Q9NR96Details
Toll-like receptor 4O00206Details