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

Title data

Scheibel, Thomas ; Weikl, Tina ; Buchner, Johannes:
Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence.
In: Proceedings of the National Academy of Sciences of the United States of America. Vol. 95 (1998) Issue 4 . - pp. 1495-1499.
ISSN 1091-6490

Official URL:

Abstract in another language

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.

Further data

Item Type:	Article in a journal
Refereed:	Yes
Institutions of the University:	Faculties Faculties > Faculty of Engineering Science Faculties > Faculty of Engineering Science > Chair Biomaterials Faculties > Faculty of Engineering Science > Chair Biomaterials > Chair Biomaterials - Univ.-Prof. Dr. Thomas Scheibel Profile Fields > Advanced Fields > Advanced Materials Profile Fields > Advanced Fields > Molecular Biosciences Profile Fields > Advanced Fields > Polymer and Colloid Science Profile Fields > Emerging Fields > Food and Health Sciences Profile Fields Profile Fields > Advanced Fields Profile Fields > Emerging Fields
Result of work at the UBT:	No
DDC Subjects:	600 Technology, medicine, applied sciences 600 Technology, medicine, applied sciences > 620 Engineering
Date Deposited:	01 Oct 2015 12:52
Last Modified:	05 Sep 2022 07:27
URI:	https://eref.uni-bayreuth.de/id/eprint/20056