Hsp90 Oligomers Interacting With The Aha1 Cochaperone: An Outlook For The Hsp90 Chaperone Machineries

The 90-kDa heat shock protein (Hsp90) is a highly flexible dimer able to self-associate in the presence of divalent cations or under heat shock. This study investigated the relationship between Hsp90 oligomers and the Hsp90 cochaperone Ahal (activator of Hsp90 ATPase). The interactions of Ahal with Hsp90 dimers and oligomers were evaluated by ultracentrifugation, size-exclusion chromatography coupled to multiangle laser light scattering and high-mass matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Hsp90 dimer was able to bind up to four Ahal molecules, and Hsp90 oligomers are also able to interact with Ahal. The binding of Ahal did not interfere with the Hsp90 oligomerization process. Except for Hsp90 dimer, the stoichiometry of the interaction remained constant, at 2 Ahal molecules per Hsp90 dimer, regardless of the degree of Hsp90 oligomerization. Moreover, Ahal predominantly bound to Hsp90 oligomers. Thus, the ability of Hsp90 oligomers to bind the Ahal ATPase activator reinforces their role within the Hsp90 chaperone machineries.