Deciphering protein cooperative interaction in pathological diseases.

It is known that, in neurodegenerative diseases, a protein can modify its conformation and thus change its pathway of interaction, reaching self-aggregation or aggregation with other molecules. The different extents of conformational changes and the types of molecular assemblies also reflect in their toxicity and could correlate with physiopathology, and in the end, with the disorder. Thus the knowledge of the biochemical and biophysical features of the proteins involved, in particular the study of the structure they acquire in presence of different partners, can give insight on the onset of the pathologies. I will present our recent results on the tau protein, involved in different neurodegenerative diseases. We used the full-length, wild-type tau, and punctual mutated isoforms comparing their course from intrinsically disordered monomers in solution to early-stage recruitment in complexes and then fibrils. We showed that diversity in the kinetics of recruitment and aggregate structure occurs from the beginning and all over their aggregative pathway. Also a change of the protein propensity of the interaction with other molecules or with the cellular membrane can act as an adjuvant in the spreading of the pathology, as we saw for p6 protein, involved in HIV-1 replication cycle.