Stability of an aggregation-prone partially folded state of human profilin-1 correlates with aggregation propensity.

ABSTRACT: A set of missense mutations in the gene encoding profilin-1 has been linked to the onset of familial forms of ALS (fALS), also known as Lou Gehrig's disease. The pathogenic potential of these mutations is linked to the formation of intracellular inclusions of the mutant proteins and correlates with the mutation-induced destabilization of its native, fully folded state. However, the mechanism by which these mutations promote misfolding and self-assembly is yet unclear. Here, using temperature-jump and stopped-flow kinetic measurements, we show that, during refolding, WT profilin-1 transiently populates a partially folded (PF) state endowed with hydrophobic clusters exposed to the solvent and with no detectable secondary structure. We observed that this conformational state is marginally sta

SUBMITTER: Del Poggetto E 

PROVIDER: S-EPMC6028969 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature