Does stability of the amyloid state depend on its biological activity?

HERRERA, MELISA; MOYANO, ALEJANDRO J.; SIRI, MACARENA; CELEJ, MARÍA S.

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica

Proteins can self-assemble into a minimum-energy conformational fibrillar structureknown as amyloid. Based on the observation that thermodynamic stability of amyloidsformed from disease-related proteins decreases with the length of the polypeptidechain, Knolwes and colleagues (Knowles et al, 2014) proposed that nature optimized300-500 residues proteins to prevent amyloid formation. The amyloid state however, isnot always at the dark side of protein world since many organisms exploit them forfunctional purposes. Therefore, we challenged the hypothesis stated above by analyzingthe thermodynamic stability of pathological, functional and generic amyloids.We worked with four different proteins: FapC (355 residues), the main component of thefunctional amyloid identified in the opportunistic pathogen Pseudomonas aeruginosa;Hpa 1 (137 residues), that forms the functional amyloid in the plant pathogenXanthomonas axonopodis pv. citri; human a-synuclein (140 residues), a neuronalpresynaptic protein responsible for the pathologic amyloid fibrils involved in Parkinson?sdisease and human serum albumin (585 residues), the most abundant protein in bloodthat carries a variety of metabolites and does not form amyloids in vivo. The amyloidsformed in vitro were characterized by Thioflavin T fluorescence, FTIR and electronmicroscopy. Then, their thermodynamic stabilities were evaluated by chemically inducedequilibrium denaturation studies. The results will be discussed in the context of the roleof the amyloid state in both health and disease.