Journal Article

DZNE-2020-07198

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dynamic Aha1 co-chaperone binding to human Hsp90.

Oroz, J. (First author)DZNE* ; Blair, L. J. ; Zweckstetter, M. (Last author)DZNE*

2019
Protein Society Bethesda, Md.

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Please use a persistent id in citations: doi:10.1002/pro.3678

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.

Keyword(s): Allosteric Regulation (MeSH) ; Binding Sites (MeSH) ; HSP90 Heat-Shock Proteins: chemistry (MeSH) ; HSP90 Heat-Shock Proteins: metabolism (MeSH) ; Humans (MeSH) ; Models, Molecular (MeSH) ; Molecular Chaperones: chemistry (MeSH) ; Molecular Chaperones: metabolism (MeSH) ; Molecular Weight (MeSH) ; Nuclear Magnetic Resonance, Biomolecular (MeSH) ; Protein Binding (MeSH) ; Protein Conformation (MeSH)

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Contributing Institute(s):

1. Structural Biology in Dementia (AG Zweckstetter)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2019

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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