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The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle.
J Mol Biol. 2004 Oct 01; 342(5):1403-13.JM

Abstract

The molecular chaperone Hsp90 mediates the ATP-dependent activation of a large number of proteins involved in signal transduction. During this process, Hsp90 was found to associate transiently with several accessory factors, such as p23/Sba1, Hop/Sti1, and prolyl isomerases. It has been shown that ATP hydrolysis triggers conformational changes within Hsp90, which in turn are thought to mediate conformational changes in the substrate proteins, thereby causing their activation. The specific role of the partner proteins in this process is unknown. Using proteins from Saccharomyces cerevisiae, we characterized the interaction of Hsp90 with its partner protein p23/Sba1. Our results show that the nucleotide-dependent N-terminal dimerization of Hsp90 is necessary for the binding of Sba1 to Hsp90 with an affinity in the nanomolar range. Two Sba1 molecules were found to bind per Hsp90 dimer. Sba1 binding to Hsp90 resulted in a decreased ATPase activity, presumably by trapping the hydrolysis state of Hsp90ATP. Ternary complexes of Hsp90Sba1 could be formed with the prolyl isomerase Cpr6, but not with Sti1. Based on these findings, we propose a model that correlates the ordered assembly of the Hsp90 co-chaperones with distinct steps of the ATP hydrolysis reaction during the chaperone cycle.

Authors+Show Affiliations

Department für Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15364569

Citation

Richter, Klaus, et al. "The Co-chaperone Sba1 Connects the ATPase Reaction of Hsp90 to the Progression of the Chaperone Cycle." Journal of Molecular Biology, vol. 342, no. 5, 2004, pp. 1403-13.
Richter K, Walter S, Buchner J. The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle. J Mol Biol. 2004;342(5):1403-13.
Richter, K., Walter, S., & Buchner, J. (2004). The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle. Journal of Molecular Biology, 342(5), 1403-13.
Richter K, Walter S, Buchner J. The Co-chaperone Sba1 Connects the ATPase Reaction of Hsp90 to the Progression of the Chaperone Cycle. J Mol Biol. 2004 Oct 1;342(5):1403-13. PubMed PMID: 15364569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle. AU - Richter,Klaus, AU - Walter,Stefan, AU - Buchner,Johannes, PY - 2004/04/13/received PY - 2004/07/16/revised PY - 2004/07/19/accepted PY - 2004/9/15/pubmed PY - 2004/11/2/medline PY - 2004/9/15/entrez SP - 1403 EP - 13 JF - Journal of molecular biology JO - J Mol Biol VL - 342 IS - 5 N2 - The molecular chaperone Hsp90 mediates the ATP-dependent activation of a large number of proteins involved in signal transduction. During this process, Hsp90 was found to associate transiently with several accessory factors, such as p23/Sba1, Hop/Sti1, and prolyl isomerases. It has been shown that ATP hydrolysis triggers conformational changes within Hsp90, which in turn are thought to mediate conformational changes in the substrate proteins, thereby causing their activation. The specific role of the partner proteins in this process is unknown. Using proteins from Saccharomyces cerevisiae, we characterized the interaction of Hsp90 with its partner protein p23/Sba1. Our results show that the nucleotide-dependent N-terminal dimerization of Hsp90 is necessary for the binding of Sba1 to Hsp90 with an affinity in the nanomolar range. Two Sba1 molecules were found to bind per Hsp90 dimer. Sba1 binding to Hsp90 resulted in a decreased ATPase activity, presumably by trapping the hydrolysis state of Hsp90ATP. Ternary complexes of Hsp90Sba1 could be formed with the prolyl isomerase Cpr6, but not with Sti1. Based on these findings, we propose a model that correlates the ordered assembly of the Hsp90 co-chaperones with distinct steps of the ATP hydrolysis reaction during the chaperone cycle. SN - 0022-2836 UR - https://www.unboundmedicine.com/medline/citation/15364569/The_Co_chaperone_Sba1_connects_the_ATPase_reaction_of_Hsp90_to_the_progression_of_the_chaperone_cycle_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(04)00892-7 DB - PRIME DP - Unbound Medicine ER -