Off-pathway aggregation can inhibit fibrillation at high protein concentrations

摘要: Ribosomal protein S6 fibrillates readily at slightly elevated temperatures and acidic pH. We find that fibrillation is retarded rather than favored when the concentration increased above a threshold of around 3.5mg/mL. name this C(FR), which retarded. Our data are consistent with model in inhibition due to formation an off-pathway oligomeric species native-like secondary structure. The dominates high concentrations but exists dynamic equilibrium monomer so seeding fibrils can overrule oligomer favors under C(FR) conditions. Thus, competes oligomers, probably monomeric conversion step required commit pathway. resistant pepsin digestion. also report forms different types dependent on concentration. observations highlight multitude conformational states available proteins destabilizing