A Zn-dependent structural transition of SOD1 modulates its ability to undergo phase separation

ABSTRACT: The misfolding and mutation of Cu/Zn superoxide dismutase (SOD1) is commonly associated with Amyotrophic lateral sclerosis (ALS). SOD1 can accumulate within stress granules (SGs), a type of membraneless organelle, which is believed to form via liquid-liquid phase separation (LLPS). Using wild type, metal deficient and different ALS disease mutants of SOD1 and computer simulations, we report here that the absence of Zn leads to structural disorder within two loop regions of SOD1, triggering SOD1 LLPS and amyloid formation. The addition of exogenous Zn to either metal-free SOD1 or to the severe ALS mutation I113T leads to stabilization of the loops and impairs SOD1 LLPS and aggregation. Moreover, partial Zn-mediated inhibition of LLPS was observed for another severe ALS mutant, G85R, which s

SUBMITTER: Dr. Krishnananda Chattopadhyay 

PROVIDER: S-SCDT-10_15252-EMBJ_2022111185 | biostudies-other |

REPOSITORIES: biostudies-other