Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins.

ABSTRACT: Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml1_53-149 and zinc-lacking Ml4_52-151. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms. Particularly, Ros87 and Ml1_53-149 appear to be much more stable to guanidine denaturation and are characterized by folding mechanisms including the presence of an intermediate. On the other hand, met

SUBMITTER: Malgieri G 

PROVIDER: S-EPMC5933289 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature