title: Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Huai
authors.forename: Huanchen
authors.initials: H
authors.lastname: Wang
authors.forename: Yudong
authors.initials: Y
authors.lastname: Liu
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Toft
authors.forename: Hengming
authors.initials: H
authors.lastname: Ke
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D018841:HSP90 Heat-Shock Proteins; D000244:Adenosine Diphosphate