Local unfolding of Cu, Zn superoxide dismutase monomer determines the morphology of fibrillar aggregates.

ABSTRACT: Aggregation of Cu, Zn superoxide dismutase (SOD1) is often found in amyotrophic lateral sclerosis patients. The fibrillar aggregates formed by wild type and various disease-associated mutants have recently been found to have distinct cores and morphologies. Previous computational and experimental studies of wild-type SOD1 suggest that the apo-monomer, highly aggregation prone, displays substantial local unfolding dynamics. The residual folded structure of locally unfolded apoSOD1 corresponds to peptide segments forming the aggregation core as identified by a combination of proteolysis and mass spectroscopy. Therefore, we hypothesize that the destabilization of apoSOD1 caused by various mutations leads to distinct local unfolding dynamics. The partially unfolded structure, exposing the hydr

SUBMITTER: Ding F 

PROVIDER: S-EPMC3320695 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature