Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. Hydrogen-exchange mass spectrometry was used to study the structural and conformational changes undergone by full-length human Hsp90beta in solution upon binding of the kinase-specific co-chaperone Cdc37 and two Hsp90 ATPase inhibitors: Radicicol and the first-generation anticancer drug DMAG. Changes in hydrogen exchange pattern in the complexes in regions of Hsp90 remote to the ligand-binding site were observed indicating long-range effects. In particular, the interface between the N-terminal domain and middle domains exhibited significant differences between the apo and complexed forms. For the inhibitors, differences in the interface between the middle domain and the C-terminal domain were also observed. These data provide important insight into the structure of the biologically active form of the protein.

Original publication

DOI

10.1016/j.jmb.2007.04.059

Type

Journal article

Journal

J Mol Biol

Publication Date

05/10/2007

Volume

372

Pages

1189 - 1203

Keywords

Amino Acid Sequence, Antineoplastic Agents, Binding Sites, Cell Cycle Proteins, Chaperonins, Enzyme Inhibitors, HSP90 Heat-Shock Proteins, Humans, Macrolides, Macromolecular Substances, Mass Spectrometry, Models, Molecular, Molecular Chaperones, Molecular Sequence Data, Protein Isoforms, Protein Structure, Tertiary