Premium
Issue Information
Publication year - 2018
Publication title -
biopolymers
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23047
Subject(s) - sod1 , chemistry , mutant , dimer , circular dichroism , mutation , biophysics , crystallography , computational biology , gene , biochemistry , biology , organic chemistry
Mutations in the Cu/Zn‐superoxide dismutase (SOD1) gene have been linked with the familial form of amyotrophic lateral sclerosis (fALS), in which misfolding and aggregation of mutant SOD1 is observed. Kumar et al . study the structure and dynamics of the ALS mutation A4V SOD1 using circular dichroism spectroscopy and molecular dynamics simulations. The mutant A4V SOD1 displays locally destabilized active site loops and unstable conformation compared to the wild‐type protein. This exposes the hydrophobic core, destabilizing the β‐barrel region and the dimer interface. These alterations result in opening of SOD1 barrel leading to misfolding and aggregation. (DOI: 10.1002/bip.23102 )