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PDBsum entry 5e85
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References listed in PDB file
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Key reference
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Title
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Close and allosteric opening of the polypeptide-Binding site in a human hsp70 chaperone bip.
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Authors
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J.Yang,
M.Nune,
Y.Zong,
L.Zhou,
Q.Liu.
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Ref.
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Structure, 2015,
23,
2191-2203.
[DOI no: ]
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PubMed id
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Abstract
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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.
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