Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery

Meyer, Philippe, Prodromou, Chrisostomos, Liao, Chunyan, Hu, Bin, Roe, S Mark, Vaughan, Cara K, Vlasic, Ignacija, Panaretou, Barry, Piper, Peter W and Pearl, Laurence H (2004) Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. EMBO Journal, 23. pp. 511-519. ISSN 0261-4189

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Abstract

Hsp90 is a molecular chaperone essential for the activation and assembly of many key eukaryotic signalling and regulatory proteins. Hsp90 is assisted and regulated by co-chaperones that participate in an ordered series of dynamic multiprotein complexes, linked to Hsp90s conformationally coupled ATPase cycle. The co-chaperones Aha1 and Hch1 bind to Hsp90 and stimulate its ATPase activity. Biochemical analysis shows that this activity is dependent on the N-terminal domain of Aha1, which interacts with the central segment of Hsp90. The structural basis for this interaction is revealed by the crystal structure of the N-terminal domain (1-153) of Aha1 (equivalent to the whole of Hch1) in complex with the middle segment of Hsp90 (273-530). Structural analysis and mutagenesis show that binding of N-Aha1 promotes a conformational switch in the middle-segment catalytic loop (370-390) of Hsp90 that releases the catalytic Arg 380 and enables its interaction with ATP in the N-terminal nucleotide-binding domain of the chaperone.

Item Type: Article
Keywords: Binding Sites, Catalysis, Genes, Suppressor, HSP90 Heat-Shock Proteins, Models, Molecular, Molecular Chaperones, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins, Sequence Alignment, Structure-Activity Relationship
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 21 Jun 2022 12:26
Last Modified: 21 Jun 2022 12:30
URI: http://sro.sussex.ac.uk/id/eprint/106483

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