Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle.

Jing Li, Klaus Richter, Jochen Reinstein, Johannes Buchner

Nature structural & molecular biology 2013 Mar

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Heat-shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that associates dynamically with various co-chaperones during its chaperone cycle. Here we analyzed the role of the activating co-chaperone Aha1 in the progression of the yeast Hsp90 chaperone cycle and identified a critical ternary Hsp90 complex containing the co-chaperones Aha1 and Cpr6. Aha1 accelerates the intrinsically slow conformational transitions of Hsp90 to an N-terminally associated state but does not fully close the nucleotide-binding pocket yet. Cpr6 increases the affinity between Aha1 and Hsp90 and further stimulates the Hsp90 ATPase activity. Synergistically, Aha1 and Cpr6 displace the inhibitory co-chaperone Sti1 from Hsp90. To complete the cycle, Aha1 is released by the co-chaperone p23. Thus, at distinct steps during the Hsp90 chaperone cycle, co-chaperones selectively trap statistically distributed Hsp90 conformers and thus turn Hsp90 into a deterministic machine.

Citation

Jing Li, Klaus Richter, Jochen Reinstein, Johannes Buchner. Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle. Nature structural & molecular biology. 2013 Mar;20(3):326-31