Hsp90 originally has been identified as one of several conserved heat-shock proteins (Hsps). Like the other major classes of Hsps, i.e. Hsp60/GroE, Hsp70, and small Hsps, Hsp90 exhibits general protective chaperone properties such as preventing the unspecific aggregation of non-native proteins. However, Hsp90 seems to be more selective than the other promiscuous general chaperones as it preferentially interacts with a specific subset of the proteome. Another specific feature of Hsp90 is its regulatory role by inducing conformational changes in folded, native-like substrate proteins that lead to their activation or stabilization. Recently the three dimensional structures of full length Hsp90 from E. coli, yeast and the endoplasmic reticulum could be solved. Together with sequence data these showed that while Hsp90 maintained its general domain structure from bacteria to man, distinct structural changes seem to have adapted Hsp90 to the more complex protein environment of the eukaryotic cell. Concomitant with the occurrence of a long charged linker connecting the N-terminal and the middle domains, the eukaryotic protein exhibits an extension of the C-terminal domain, which includes the conserved amino acid motif MEEVD at the C-terminus. This region serves as the major interaction site for a cohort of co-chaperones, which apparently support Hsp90 in the folding and activation of its substrate proteins in eukaryotes. In this review, we summarize the current knowledge on the functional principles of this molecular machine including the ATP-driven chaperone cycle of Hsp90 and its regulation by co-chaperones and posttranslational modifications.

• PMID: 18442971
• DOI full text
• PubMed

Reference Type

Journal Article | Research Support, Non-U.S. Gov't | Review

Authors

Wandinger SK, Richter K, Buchner J

Primary Lit For

Additional Lit For

Review For