Structural analysis of substrate binding by the molecular chaperone DnaK

被引:1031
作者
Zhu, XT
Zhao, X
Burkholder, WF
Gragerov, A
Ogata, CM
Gottesman, ME
Hendrickson, WA
机构
[1] COLUMBIA UNIV, HOWARD HUGHES MED INST, NEW YORK, NY 10032 USA
[2] COLUMBIA UNIV, CANC RES INST, NEW YORK, NY 10032 USA
[3] BROOKHAVEN NATL LAB, NATL SYNCHROTRON LIGHT SOURCE, HOWARD HUGHES MED INST, STONY BROOK, NY USA
关键词
D O I
10.1126/science.272.5268.1606
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DnaK and other members of the 70-kilodalton heat-shock protein (hsp70) family promote protein folding, interaction, and translocation, both constitutively and in response to stress, by binding to unfolded polypeptide segments. These proteins have two functional units: a substrate-binding portion binds the polypeptide, and an adenosine triphosphatase portion facilitates substrate exchange. The crystal structure of a peptide complex with the substrate-binding unit of DnaK has now been determined at 2.0 Angstrom resolution. The structure consists of a beta-sandwich subdomain followed by alpha-helical segments. The peptide is bound to DnaK in an extended conformation through a channel defined by loops from the beta sandwich. An alpha-helical domain stabilizes the complex, but does not contact the peptide directly. This domain is rotated in the molecules of a second crystal lattice, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.
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页码:1606 / 1614
页数:9
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