TLR7/8/9 ATP-bound Gp96 dimer:CNPY3:TLR7/8/9 Apo-GP96 dimer TLR folding by chaperones GP96 and CNPY3 Authored: Shamovsky, V, 2011-10-19 Edited: Shamovsky, V, 2012-02-19 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).<p>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). Pubmed17275357 Pubmed18509083 Pubmed19965672 Pubmed20865800 Pubmed22223641 Pubmed8344253 Reactome Database ID Release 431678923 Reactome, http://www.reactome.org ReactomeREACT_118729 Reviewed: Gillespie, ME, 2012-02-09 Reviewed: Leifer, CA, Rose II, WA, 2012-02-28 has a Stoichiometric coefficient of 2