Structural highlights
Disease
[GRP78_HUMAN] Note=Autoantigen in rheumatoid arthritis.[1]
Function
[GRP78_HUMAN] Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER.[2]
Publication Abstract from PubMed
Binding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. BiP contains two functional domains: a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. Although crucial to the chaperone activity, the molecular mechanisms of polypeptide binding and allosteric coupling of BiP are poorly understood. Here, we present crystal structures of an intact human BiP in the ATP-bound state, the first intact eukaryotic Hsp70 structure, and isolated BiP-SBD with a peptide substrate bound representing the ADP-bound state. These structures and our biochemical analysis demonstrate that BiP has a unique NBD-SBD interface that is highly conserved only in eukaryotic Hsp70s found in the cytosol and ER to fortify its ATP-bound state and promote the opening of its polypeptide-binding pocket.
Close and Allosteric Opening of the Polypeptide-Binding Site in a Human Hsp70 Chaperone BiP.,Yang J, Nune M, Zong Y, Zhou L, Liu Q Structure. 2015 Dec 1;23(12):2191-203. doi: 10.1016/j.str.2015.10.012. Epub 2015 , Nov 19. PMID:26655470[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Corrigall VM, Bodman-Smith MD, Fife MS, Canas B, Myers LK, Wooley P, Soh C, Staines NA, Pappin DJ, Berlo SE, van Eden W, van Der Zee R, Lanchbury JS, Panayi GS. The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol. 2001 Feb 1;166(3):1492-8. PMID:11160188
- ↑ Dana RC, Welch WJ, Deftos LJ. Heat shock proteins bind calcitonin. Endocrinology. 1990 Jan;126(1):672-4. PMID:2294010
- ↑ Yang J, Nune M, Zong Y, Zhou L, Liu Q. Close and Allosteric Opening of the Polypeptide-Binding Site in a Human Hsp70 Chaperone BiP. Structure. 2015 Dec 1;23(12):2191-203. doi: 10.1016/j.str.2015.10.012. Epub 2015 , Nov 19. PMID:26655470 doi:http://dx.doi.org/10.1016/j.str.2015.10.012
