Structural changes to monomeric CuZn superoxide dismutase caused by the familial amyotrophic lateral sclerosis-associated mutation A4V.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease, and the inherited form, familial ALS (fALS), has been linked to over 100 different point mutations scattered throughout the Cu-Zn superoxide dismutase protein (SOD1). The disease is likely due to a toxic gain of function caused by the misfolding, oligomerization, and eventual aggregation of mutant SOD1, but it is not yet understood how the structurally diverse mutations result in a common disease phenotype. The behavior of the apo-monomer fALS-associated mutant protein A4V was explored using molecular-dynamics simulations to elucidate characteristic structural changes to the protein that may allow the mutant form to improperly associate with other monomer subunits. Simulations showed that the mutant pro

SUBMITTER: Schmidlin T 

PROVIDER: S-EPMC2749781 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature