On the effect of trimethylamine N-oxide on the conformational equilibrium of the chaperone Hsp90

The chaperone Hsp90 is a dimeric protein that populates two different conformations at room temperature in aqueous solution: an open and a closed one, related by rigid body domain reorientation. The former is favoured in neat water, whereas the latter is favoured in aqueous 1 M trimethylamine N-oxide (TMAO) solution. The two conformations, having a different shape, possess a different water accessible surface area, and so give rise to a different solvent-excluded volume effect. TMAO favours the closed conformation because its addition to water causes an increase in the magnitude of the solvent-excluded volume effect due to the density increase.