Reactome | TLR folding by chaperones GP96 and CNPY3

TLR folding by chaperones GP96 and CNPY3

Stable Identifier

R-HSA-1678923

Type

Reaction [binding]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen, endoplasmic reticulum membrane

ReviewStatus

5/5

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TLR folding by chaperones GP96 and CNPY3

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GP96 (also known as GRP94, HSP90b1), a paralogue of HSP90 in the endoplasmic reticulum, acts as a chaperone for some integrines and Toll-like receptors. Macrophages or B-cells from gp96 knockout mice have abrogated function of TLR2, 4, 5, 7 and 9, but not TLR3 (Yang Y et al 2007, Liu B and Li Z 2008, Staron M et al 2010). GP96 interacts with TLRs and integrines via its C-terminal hydrophobic domain, formed by residues 652-678 (Wu S et al 2012). GP96 functions as a V-shaped dimer in ATP-dependent manner, however it remains unclear how ATP hydrolysis-dependent conformational changes of GP96 are regulated (Li Z and Srivastava PK 1993).

GP96 forms a complex with co-chaperone CNPY3, also known as PRAT4A. GP96-CNPY3 promotes the proper post-translational ectodomain folding of TLRs, but not TLR3 (Liu B et al 2010).

Literature References

PubMed ID	Title	Journal	Year
18509083	Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin Liu, B, Li, Z	Blood	2008
17275357	Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages Dai, J, Liu, B, Lefrançois, L, Srivastava, PK, Yang, Y, Zammit, DJ, Li, Z	Immunity	2007
22223641	The Molecular Chaperone gp96/GRP94 Interacts With Toll-Like Receptors And Integrins Via Its C-Terminal Hydrophobic Domain Guo, B, Liu, B, Gewirth, D, Wu, S, Hong, F, Li, Z	J Biol Chem	2012
20865800	Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone Bona, R, Staron, M, Liu, B, Han, D, Li, Y, Qiu, Z, Yang, Y, Hao, B, Wu, S, Hong, F, Li, Z, Li, Y	Nat Commun	2010
8344253	Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation Srivastava, PK, Li, Z	EMBO J	1993
19965672	gp96, an endoplasmic reticulum master chaperone for integrins and Toll-like receptors, selectively regulates early T and B lymphopoiesis Aguila, HL, Li, J, Liu, B, Staron, M, Yang, Y, Shen, Y, Zúñiga-Pflücker, JC, Li, Z, Goldschneider, I	Blood	2010