Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90.
The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity.
Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.
Jian
J
Li
Lihua
L
Sun
Chunyan
C
Xu
Feng
F
Yu
Huan
H
Zhou
Yanlong
Y
Zhao
Jian
J
Zhang
Jianhua
J
Cai
Cheney
C
Mao
Lin
L
Tang
Yechun
Y
Xu
Jianhua
J
He
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D018841:HSP90 Heat-Shock Proteins; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate