%0 Journal Article
%A Oroz, Javier
%A Blair, Laura J
%A Zweckstetter, Markus
%T Dynamic Aha1 co-chaperone binding to human Hsp90.
%J Protein science
%V 28
%N 9
%@ 0961-8368
%C Bethesda, Md.
%I Protein Society
%M DZNE-2020-07198
%P 1545-1551
%D 2019
%X 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.
%K Allosteric Regulation
%K Binding Sites
%K HSP90 Heat-Shock Proteins: chemistry
%K HSP90 Heat-Shock Proteins: metabolism
%K Humans
%K Models, Molecular
%K Molecular Chaperones: chemistry
%K Molecular Chaperones: metabolism
%K Molecular Weight
%K Nuclear Magnetic Resonance, Biomolecular
%K Protein Binding
%K Protein Conformation
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31299134
%2 pmc:PMC6699087
%R 10.1002/pro.3678
%U https://pub.dzne.de/record/140876