Dynamic Aha1 co-chaperone binding to human Hsp90.

Oroz, J.; Blair, L. J.; Zweckstetter, M.

doi:10.1002/pro.3678

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Dynamic Aha1 co-chaperone binding to human Hsp90.

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Zweckstetter, M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Citation

Oroz, J., Blair, L. J., & Zweckstetter, M. (2019). Dynamic Aha1 co-chaperone binding to human Hsp90. Protein Science, 28(9), 1545-1551. doi:10.1002/pro.3678.

Cite as: https://hdl.handle.net/21.11116/0000-0004-41CC-D

Abstract

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.