Abstract：
:In eukaryotes, the essential dimeric molecular chaperone Hsp90 is required for the activation and maturation of specific substrates such as steroid hormone receptors, tyrosine kinases and transcription factors. Hsp90 is involved in the establishment of cancer and has become an attractive target for drug design. Here we present a structural characterization of the complex between Hsp90 and the tumor suppressor p53, a key mediator of apoptosis whose structural integrity is crucial for cell-cycle control. Using biophysical methods, we show that the human p53 DNA-binding domain interacts with multiple domains of yeast Hsp90. p53 binds to the Hsp90 C-terminal domain in its native-like state in a charge-dependent manner, but it also associates weakly with binding sites in the middle and the N-terminal domains. The fine-tuned interplay between several Hsp90 domains provides the interactions required for efficient chaperoning of p53.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Hagn F,Lagleder S,Retzlaff M,Rohrberg J,Demmer O,Richter K,Buchner J,Kessler Hdoi
10.1038/nsmb.2114subject
Has Abstractpub_date
2011-09-04 00:00:00pages
1086-93issue
10eissn
1545-9993issn
1545-9985pii
nsmb.2114journal_volume
18pub_type
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