Oligomeric state and chaperon activity of Hsp60.

Abstract

Heat-shock proteins are capable to exert their stabilizing action against biomolecules aggregation through different mechanisms, which are generally related to their molecular weight. Similar to its bacterial homologous GroEl, Hsp60 is known to work as a folding machine with the assistance of co-chaperonin Hsp10 and ATP. However, recent experimental evidence suggested an alternative mechanism exploited by Hsp60 towards aggregation prone molecules. Indeed, we already observed that Hsp60 stabilized Aβ40 against fibrillization in the absence of ATP by recruiting early small aggregates of Ab, Here we investigate the mechanism exerted by Hsp60 against the amyloid fibrillization in relation with its oligomeric structure. To this purpose, the monomeric or tetradecameric form of the protein were isolated and their effect on beta-amyloid aggregation was tested separately. The structural stability of the two forms of Hsp60 was also investigated by differential scanning calorimetry (DSC), Light Scattering and Circular Dichroism. Results shown that the monomeric form is less stable but more effective against amyloid fibrillization. A major functionality related to a less ordered and stable structure is a common treat of proteins having intrinsically disordered regions (IDR). In Hsp60 contacts between subunits in the equatorial domain have been recognized as the region of moonlighting character. Their exposure to the solvent confers to monomeric Hsp60 the ability to interact with amyloid molecules at a major extent than that due to the plain increase of the total protein surface.