Common dynamical signatures of familial amyotrophic lateral sclerosis-associated structurally diverse Cu, Zn superoxide dismutase mutants.

ABSTRACT: More than 100 structurally diverse point mutations leading to aggregation in the dimeric enzyme Cu, Zn superoxide dismutase (SOD1) are implicated in familial amyotrophic lateral sclerosis (FALS). Although SOD1 dimer dissociation is a known requirement for its aggregation, the common structural basis for diverse FALS mutations resulting in aggregation is not fully understood. In molecular dynamics simulations of wild-type SOD1 and three structurally diverse FALS mutants (A4V, G37R, and H46R), we find that a common effect of mutations on SOD1 dimer is the mutation-induced disruption of dynamic coupling between monomers. In the wild-type dimer, the principal coupled motion corresponds to a "breathing motion" of the monomers around an axis parallel to the dimer interface, and an opening-closin

SUBMITTER: Khare SD 

PROVIDER: S-EPMC1413921 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature