The complex dance of the molecular chaperone Hsp90

Abstract

Hsp90 chaperone function requires traversal of a nucleotide-dependent conformational cycle, but the slow and variable rate of Hsp90-mediated ATP hydrolysis is difficult to envision as a determinant of conformational change. A recent study solves this dilemma by showing that Hsp90 samples multiple conformational states in the absence of nucleotides, which serve to influence, but not direct, the cycle. The conformational program of Hsp90 is conserved from bacteria to humans, although the population dynamics are species specific.

Figure 1.

Species-dependent conformational equilibrium model for the Hsp90 molecular chaperone cycle. Whereas E. coli Hsp90 (gray), yeast Hsp90 (blue) and human Hsp90 (red) all can be found to occupy an ‘open’ (apo), ‘closed’ (ATP) and ‘compact’ (ADP) conformation; steady-state occupancy of each conformation is a unique characteristic of each species. Nonetheless, multiple conformational states are sampled to one degree or another by the apo-Hsp90s in each species. N-, M- and C-domains are labeled as shown; individual Hsp90 protomers are colored brown or green, respectively.