Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP. Qi, R F, Sarbeng, E B, Liu, Q, Le, K Q, Xu, X P, Xu, H Y, Yang, J, Wong, J L, Vorvis, C, Hendrickson, W A, Zhou, L, & Liu, Q L Nature Structural & Molecular Biology, 20(7):900–907, 2013. doi abstract bibtex 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-angstrom resolution. The ATP-bound NBD adopts a unique conformation, forming extensive interfaces with an SBD that has changed radically, having its alpha-helical lid displaced and the polypeptide-binding channel of its beta-subdomain restructured. These conformational changes, together with our biochemical assays, provide a structural explanation for allosteric coupling in Hsp70 activity.
@article{qi_allosteric_2013,
title = {Allosteric opening of the polypeptide-binding site when an {Hsp70} binds {ATP}},
volume = {20},
doi = {Doi 10.1038/Nsmb.2583},
abstract = {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-angstrom resolution. The ATP-bound NBD adopts a unique conformation, forming extensive interfaces with an SBD that has changed radically, having its alpha-helical lid displaced and the polypeptide-binding channel of its beta-subdomain restructured. These conformational changes, together with our biochemical assays, provide a structural explanation for allosteric coupling in Hsp70 activity.},
language = {English},
number = {7},
journal = {Nature Structural \& Molecular Biology},
author = {Qi, R F and Sarbeng, E B and Liu, Q and Le, K Q and Xu, X P and Xu, H Y and Yang, J and Wong, J L and Vorvis, C and Hendrickson, W A and Zhou, L and Liu, Q L},
year = {2013},
keywords = {conformational-changes, crystal-structure, interdomain communication, molecular chaperone dnak, peptide-binding, shock cognate protein, structural basis, structure validation, substrate-binding, wild-type},
pages = {900--907},
}
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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-angstrom resolution. The ATP-bound NBD adopts a unique conformation, forming extensive interfaces with an SBD that has changed radically, having its alpha-helical lid displaced and the polypeptide-binding channel of its beta-subdomain restructured. 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