T54R mutation destabilizes the dimer of superoxide dismutase 1^T54R by inducing steric clashes at the dimer interface.

ABSTRACT: Mutations cause abnormalities in protein structure, function and oligomerization. Different mutations in the superoxide dismutase 1 (SOD1) protein cause its misfolding, loss of dimerization and aggravate its aggregation in the amyotrophic lateral sclerosis disease. In this study, we report the mechanistic details of how a threonine-to-arginine mutation at the 54^th position (T54R) of SOD1 results in destabilization of the dimer interface of SOD1^T54R. Using computational and experimental methods, we show that the T54R mutation increases fluctuation of the mutation-harboring loop (R54-loop) of SOD1^T54R. Fluctuation of this loop causes steric clashes that involve arginine-54 (R54) and other residues of SOD1^T54R, resulting in loss of inter-subunit con

SUBMITTER: Ghosh DK 

PROVIDER: S-EPMC9050410 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature