TY  - JOUR
AU  - Oroz, Javier
AU  - Blair, Laura J
AU  - Zweckstetter, Markus
TI  - Dynamic Aha1 co-chaperone binding to human Hsp90.
JO  - Protein science
VL  - 28
IS  - 9
SN  - 0961-8368
CY  - Bethesda, Md.
PB  - Protein Society
M1  - DZNE-2020-07198
SP  - 1545-1551
PY  - 2019
AB  - 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.
KW  - Allosteric Regulation
KW  - Binding Sites
KW  - HSP90 Heat-Shock Proteins: chemistry
KW  - HSP90 Heat-Shock Proteins: metabolism
KW  - Humans
KW  - Models, Molecular
KW  - Molecular Chaperones: chemistry
KW  - Molecular Chaperones: metabolism
KW  - Molecular Weight
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Protein Binding
KW  - Protein Conformation
LB  - PUB:(DE-HGF)16
C6  - pmid:31299134
C2  - pmc:PMC6699087
DO  - DOI:10.1002/pro.3678
UR  - https://pub.dzne.de/record/140876
ER  -