5E86

isolated SBD of BiP with loop34 modification

Summary for 5E86

• Entry DOI: 10.2210/pdb5e86/pdb
• Related: 5E84 5E85
• Descriptor: 78 kDa glucose-regulated protein (2 entities in total)
• Functional Keywords: molecular chaperones;hsp70;bip;protein folding;endoplasmic reticulum;allosteric coupling, chaperone
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 26029.45

Authors

Liu, Q.,Yang, J.,Nune, M.,Zong, Y.,Zhou, L. (deposition date: 2015-10-13, release date: 2015-12-30, Last modification date: 2024-03-06)

Primary citation

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, 23:2191-2203, 2015

PubMed Abstract: 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.

PubMed: 26655470
DOI: 10.1016/j.str.2015.10.012

Experimental method

X-RAY DIFFRACTION (2.681 Å)