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EVIDENCE THAT THE NOVOBIOCIN‐SENSITIVE ATP‐BINDING SITE OF THE HEAT SHOCK PROTEIN 90 (HSP90) IS NECESSARY FOR ITS AUTOPHOSPHORYLATION
Author(s) -
Langer T.,
Schlatter H.,
Fasold H.
Publication year - 2002
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.2002.0882
Subject(s) - geldanamycin , autophosphorylation , hsp90 , novobiocin , heat shock protein , binding site , biochemistry , microbiology and biotechnology , biology , chemistry , biophysics , phosphorylation , protein kinase a , gene , antibiotics
The 90kDa heat shock protein (Hsp90) is one of the most abundant protein and essential for all eukaryotic cells. Many proteins require the interaction with Hsp90 for proper function. Upon heat stress the expression level of Hsp90 is even enhanced. It is assumed, that under these conditions Hsp90 is required to protect other proteins from aggregation. One property of Hsp90 is its ability to undergo autophosphorylation. The N‐terminal domain of Hsp90 has been shown to contain an unusual ATP‐binding site. A well‐known inhibitor of Hsp90 function is geldanamycin binding to the N‐terminal ATP‐binding site with high affinity. Recently it was shown that Hsp90 possesses a second ATP‐binding site in the C‐terminal region, which can be competed with novobiocin. Autophosphorylation of Hsp90 was analysed by incubation with γ 32 P‐ATP. Addition of geldanamycin did not interfere with the capability for autophosphorylation, while novobiocin indeed did. These results suggest that the C‐terminal ATP‐binding site is required for autophosphorylation of Hsp90.