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PDBsum entry 4jn4
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References listed in PDB file
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Key reference
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Title
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Allosteric opening of the polypeptide-Binding site when an hsp70 binds ATP.
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Authors
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R.Qi,
E.B.Sarbeng,
Q.Liu,
K.Q.Le,
X.Xu,
H.Xu,
J.Yang,
J.L.Wong,
C.Vorvis,
W.A.Hendrickson,
L.Zhou,
Q.Liu.
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Ref.
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Nat Struct Biol, 2013,
20,
900-907.
[DOI no: ]
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PubMed id
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Abstract
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The 70-kilodalton (kDa) heat-shock proteins (Hsp70s) are ubiquitous molecular
chaperones essential for cellular protein folding and proteostasis. Each Hsp70
has two functional domains: a nucleotide-binding domain (NBD), which binds and
hydrolyzes ATP, and a substrate-binding domain (SBD), which binds extended
polypeptides. NBD and SBD interact little when in the presence of ADP; however,
ATP binding allosterically couples the polypeptide- and ATP-binding sites. ATP
binding promotes polypeptide release; polypeptide rebinding stimulates ATP
hydrolysis. This allosteric coupling is poorly understood. Here we present the
crystal structure of an intact ATP-bound Hsp70 from Escherichia coli at 1.96-Å
resolution. The ATP-bound NBD adopts a unique conformation, forming extensive
interfaces with an SBD that has changed radically, having its α-helical lid
displaced and the polypeptide-binding channel of its β-subdomain restructured.
These conformational changes, together with our biochemical assays, provide a
structural explanation for allosteric coupling in Hsp70 activity.
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