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Hsp90 is an essential chaperone that requires large allosteric changes to determine its ATPase activity and client binding. The co-chaperone Aha1, which is the major ATPase stimulator in eukaryotes, is important for regulation of Hsp90's allosteric timing. Little is known, however, about the structure of the Hsp90/Aha1 complex. Here, we characterize the solution structure of unmodified human Hsp90/Aha1 complex using NMR spectroscopy. We show that the 214-kDa complex forms by a two-step binding mechanism and adopts multiple conformations in the absence of nucleotide. Aha1 induces structural changes near Hsp90's nucleotide-binding site, providing a basis for its ATPase-enhancing activity. Our data reveal important aspects of this pivotal chaperone/co-chaperone interaction and emphasize the relevance of characterizing dynamic chaperone structures in solution. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Protein science : a publication of the Protein Society
Hsp90 is a crucial chaperone whose ATPase activity is fundamental for stabilizing and activating a diverse array of client proteins. Binding and hydrolysis of ATP by dimeric Hsp90 drives a conformatio...
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Heat-shock proteins (HSP) have been very highly conserved throughout the evolution of species and are characterized by their chaperone function, thanks to their ability to prevent aggregat...
A class of MOLECULAR CHAPERONES whose members act in the mechanism of SIGNAL TRANSDUCTION by STEROID RECEPTORS.
A histone chaperone protein that plays a role in the deposition of NUCLEOSOMES on newly synthesized DNA. It is comprised of three different subunits of 48, 60, and 150 kDa molecular size. The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling.
A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain. Runx1 is frequently mutated in human LEUKEMIAS.
Systematic study of the body and the use of its static and dynamic position as a means of communication.
Post-transcriptional regulatory proteins required for the accumulation of mRNAs that encode the gag and env gene products in HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The rex (regulator x; x is undefined) products act by binding to elements in the LONG TERMINAL REPEAT.