Between the large class of molecules that maintain protein homeostasis, called molecular chaperones, a subclass that speciﬁcally assist, in an ATP-dependent manner, the correct folding of newly synthesized proteins is constituted by chaperonins. Among them, Hsp60 consists of a double heptameric ring structure with a large central cavity, closed by the co-chaperonin Hsp10, where the unfolded protein binds via hydrophobic interactions. Hsp60 is typically located in the mitochondria, but in some pathological situations it accumulates in the cytoplasm. In these cases, cytoplasmatic Hsp60 results as a mixture of naïvechaperonin, never entered the organella, and mitochondrial one secreted from them upon stress, lacking the import signal sequence1. Information about these chaperonins’ structure and stability in solution are very recent2 and still incomplete, probably because of their close resemblance to its well-known bacterial homologue GroEL3,4. Nevertheless, Hsp60 deserves particular interest as a consequence of its role in neurodegenerative disorders, since it is able to inhibit the formation of amyloid-β peptide fibrils, hallmark of Alzheimer’s disease5. We present an investigation on Hsp60 structure and stability against chemical denaturant performed by molecular dynamics (MD), circular dichroism (CD) and small-angle X-ray scattering (SAXS). In particular, self-organization of naïve and mitochondrial Hsp60 in solution have been studied in comparison with bacterial GroEL. The resulting unfolding free energy, as well as the oligomerization process dependence on denaturant concentration, have been obtained and represent promising tools for a deeper understanding of Hsp60 functionality and for the discover of its potentiality for medical applications.
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2S. Nisemblatet et al., Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 70, 116-119 (2014);
3S. Vilasi et al., Plos One, 9, 5 (2014);
4Spinello et al., RSC Advances, 62 (2015);
5T. Hoshino et al., The Journal of Neuroscience, 31, 5225-5234 (2011).