DOI: 10.1073/pnas.95.4.1495. Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence

Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence

10.1073/pnas.95.4.1495

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The abundant molecular chaperone Hsp90 is a key regulator of protein structure in the cytosol of eukaryotic cells. Although under physiological conditions a specific subset of proteins is substrate for Hsp90, under stress conditions Hsp90 seems to perform more general functions. However, the underlying mechanism of Hsp90 remained enigmatic. Here, we analyzed the function of conserved Hsp90 domains. We show that Hsp90 possesses two chaperone sites located in the N- and C-terminal fragments, respectively. The C-terminal fragment binds to partially folded proteins in an ATP-independent way potentially regulated by cochaperones. The N-terminal domain contains a peptide binding site that seems to bind preferentially peptides longer than 10 amino acids. Peptide dissociation is induced by ATP binding. Furthermore, the antitumor drug geldanamycin both inhibits the weak ATPase of Hsp90 and stimulates peptide release. We propose that the existence of two functionally different chaperone sites together with a substrate-selecting set of cochaperones allows Hsp90 to guide the folding of a subset of target proteins and, at the same time, to exhibit general chaperone functions.

Bibliography

Scheibel, T., Weikl, T., & Buchner, J. (1998). Two chaperone sites in Hsp90 differing in substrate specificity andâATPâdependence. Proceedings of the National Academy of Sciences, 95(4), 1495â1499.

Authors 3

Thomas Scheibel (first)
Tina Weikl (additional)
Johannes Buchner (additional)

References 32 Referenced 205

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:44 p.m.)
Indexed	3 weeks, 3 days ago (Aug. 2, 2025, 12:21 a.m.)
Issued	27 years, 6 months ago (Feb. 17, 1998)
Published	27 years, 6 months ago (Feb. 17, 1998)
Published Online	27 years, 6 months ago (Feb. 17, 1998)
Published Print	27 years, 6 months ago (Feb. 17, 1998)

Funders 0

None

BibTeX

@article{Scheibel_1998, title={Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.4.1495}, DOI={10.1073/pnas.95.4.1495}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Scheibel, Thomas and Weikl, Tina and Buchner, Johannes}, year={1998}, month=feb, pages={1495–1499} }

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