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

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

The molecular chaperone gp96/GRP94 interacts with Toll-like receptors and integrins via its C-terminal hydrophobic domain.

The structural basis for molecular chaperones to discern misfolded proteins has long been an enigma. As the endoplasmic reticulum paralogue of the cytosolic HSP90, gp96 (GRP94, HSP90b1) is an essential molecular chaperone for Toll-like receptors (TLRs) and integrins. However, little is known about its client-binding domain (CBD). Herein, we provide genetic and biochemical evidence to definitive...

Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90

Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins ...

An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response.

Heat shock protein (HSP) gp96, or grp94 is an endoplasmic reticular (ER) paralog of the cytosolic HSP90. Being abundant and non-polymorphic, gp96 plays significant roles in maintaining protein homeostasis in the secretory pathway. This "house-keeping" role of gp96 has now been overshadowed by the intriguing findings that gp96 modulates both the innate and adaptive components of the immune syste...

A Primate Specific Extra Domain in the Molecular Chaperone Hsp90

Hsp90 (heat shock protein 90) is an essential molecular chaperone that mediates folding and quality control of client proteins. Many of them such as protein kinases, steroid receptors and transcription factors are involved in cellular signaling processes. Hsp90 undergoes an ATP hydrolysis dependent conformational cycle to assist folding of the client protein. The canonical Hsp90 shows a typical...