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          Institute: MPI für medizinische Forschung     Collection: Jahbruch 2014_archival     Display Documents

ID: 681454.0, MPI für medizinische Forschung / Jahbruch 2014_archival
Cdc37 (Cell division dycle 37) restricts Hsp90 (Heat shock protein 90) motility by interaction with N−terminal and middle domain binding sites
Translation of Title:Cdc37 (Cell division dycle 37) restricts Hsp90 (Heat shock protein 90) motility by interaction with N−terminal and middle domain binding sites
Authors:Eckl, Julia M.; Rutz, Daniel A.; Haslbeck, Veronika; Zierer, Bettina K.; Reinstein, Jochen; Richter, Klaus
Date of Publication (YYYY-MM-DD):2013-05-31
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J. Biol. Chem.
Issue / Number:22
Start Page:16032
End Page:16042
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:The ATPase−driven dimeric molecular Hsp90 (heat shock protein 90) and its cofactor Cdc37 (cell division cycle 37 protein) are crucial to prevent the cellular depletion of many protein kinases. In complex with Hsp90, Cdc37 is thought to bind an important lid structure in the ATPase domain of Hsp90 and inhibit ATP turnover by Hsp90. As different interaction modes have been reported, we were interested in the interaction mechanism of Hsp90 and Cdc37. We find that Cdc37 can bind to one subunit of the Hsp90 dimer. The inhibition of the ATPase activity is caused by a reduction in the closing rate of Hsp90 without obviously bridging the two subunits or affecting nucleotide accessibility to the binding site. Although human Cdc37 binds to the N−terminal domain of Hsp90, nematodal Cdc37 preferentially interacts with the middle domain of CeHsp90 and hHsp90, exposing two Cdc37 interaction sites. A previously unreported site in CeCdc37 is utilized for the middle domain interaction. Dephosphorylation of CeCdc37 by the Hsp90−associated phosphatase PPH−5, a step required during the kinase activation process, proceeds normally, even if only the new interaction site is used. This shows that the second interaction site is also functionally relevant and highlights that Cdc37, similar to the Hsp90 cofactors Sti1 and Aha1, may utilize two different attachment sites to restrict the conformational freedom and the ATP turnover of Hsp90
Free Keywords:Analytical Ultracentrifugation, Co−chaperone, Molecular Chaperone, Nucleotide, Protein Conformation, Protein−Protein Interactions
External Publication Status:published
Document Type:Article
Communicated by:wkaiser
Affiliations:MPI für medizinische Forschung/Abteilung Biomolekulare Mechanismen
MPI für medizinische Forschung/Abteilung Biomolekulare Mechanismen/Molecular chaperones
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