A switch point in the molecular chaperone Hsp90 responding to client interaction.

Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes large conformational changes during its functional cycle. It has been established that conformational switch points exist in the N-terminal (Hsp90-N) and C-terminal (Hsp90-C) domains of Hsp90, however information for switch points in the large middle-domain (Hsp90-M) is scarce. ...
Here we report on a tryptophan residue in Hsp90-M as a new type of switch point. Our study shows that this conserved tryptophan senses the interaction of Hsp90 with a stringent client protein and transfers this information via a cation-Ï€ interaction with a neighboring lysine. Mutations at this position hamper the communication between domains and the ability of a client protein to affect the Hsp90 cycle. The residue thus allows Hsp90 to transmit information on the binding of a client from Hsp90-M to Hsp90-N which is important for progression of the conformational cycle and the efficient processing of client proteins.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Amino Acid Substitution, Animals, Binding Sites, Caenorhabditis elegans, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli, Gene Expression, Genetic Vectors, HSP90 Heat-Shock Proteins, Humans, Ligands, Lysine, Mice, Molecular Dynamics Simulation, Mutation, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Recombinant Proteins, Saccharomyces cerevisiae, Sequence Alignment, Structural Homology, Protein, Tryptophan, Zebrafish
Nat Commun
Date: Dec. 16, 2017
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