Changes in Hsp90 Accompanying the ATPase Cycle

Conformational Changes in Hsp90 Accompanying the ATPase Cycle 

Hsp90 forms a stable complex with the co-chaperone p23/Sbal (Fang et al., 1998 Johnson and Toft, 1994 1995) in the presence of non-hydrolyzable ATP analogs, such as AMP-PNP. Such a stable complex can also be formed by incubation with ATP in the presence of molybdate ions in which a stable Hsp90—ADP—MoO - complex is progressively formed. Molybdate has long been included in Hsp90 buffers, prior to 

Observation of Hsp90 dimers using rotary-shadowing electron microscopy has shown an essentially elongated structure in which the C-termini formed a dimeric interaction while the N-termini were dissociated, as in the relaxed state described above. Subsequently, formation of structures in which both N- and C-termini appeared to be in proximity was observed following severe heat shock or, less effectively, in the 

The nature and location of the client protein interaction with Hsp90 are obscure. Deletion studies suggest that the C-terminal region, implicated in dimerization and co-chaperone recruitment, was also involved in client-protein interaction (Shaknovich et al., 1992 Sullivan and Toft, 

Hsp90 ATPase Inhibitors—A New Class of Antitumor Drugs 

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IV. Conformational Changes in Hsp90 Accompanying the ATPase Cycle. 166... 

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