Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding.
Hsp90 is an abundant molecular chaperone involved in many biological systems. We report here the crystal structures of the unliganded and ADP bound fragments containing the N-terminal and middle domains of HtpG, an E. coli Hsp90. These domains are not connected through a flexible linker, as often portrayed in models, but are intimately associated with one another. The individual HtpG domains have similar folding to those of DNA gyrase B but assemble differently, suggesting somewhat different mechanisms for the ATPase superfamily. ADP binds to a subpocket of a large site that is jointly formed by the N-terminal and middle domains and induces conformational changes of the N-terminal domain. We speculate that this large pocket serves as a putative site for binding of client proteins/cochaperones. Modeling shows that ATP is not exposed to the molecular surface, thus implying that ATP activation of hsp90 chaperone activities is accomplished via conformational changes.
Huai
Qing
Q
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Wang
Huanchen
H
Liu
Yudong
Y
Kim
Hwa-Young
HY
Toft
David
D
Ke
Hengming
H
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers; D004926:Escherichia coli / Q000737:chemistry*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D017931:DNA Primers; D018841:HSP90 Heat-Shock Proteins; D000244:Adenosine Diphosphate