One mechanism to fine-tune the molecular chaperone Hsp90 is by allosteric regulation points, but how this mechanism works in Hsp90 is not understood yet.

To analyze the allosteric regulation mechanism in Hsp90, we used a combined approach of molecular dynamics simulations (revealing the allosteric regulation points) and biochemical assays (probing these sites in vitro and in vivo).

Our findings explain for the first time how allosteric regulation works within Hsp90: activating regulation points loosen and inhibiting regulation points ridgify the protein.

The effects of allosteric regulation points can be overcome by the Hsp90 co-chaperones as the next layer of regulation.