Pathogenic R₁₆₃W Variant of the Copper Chaperone for Sod1 (Ccs) Functions as an Anti-chaperone.

ABSTRACT: The copper chaperone for Sod1 (Ccs) is a metallochaperone that plays a multifaceted role in the maturation of Cu,Zn superoxide dismutase (Sod1). The Ccs mutation R₁₆₃W was identified in an infant with fatal neurological abnormalities. Based on a comprehensive structural and functional analysis, we developed the first data-driven model for R₁₆₃W-related pathogenic phenotypes. The work here confirms previous findings that the substitution of arginine with tryptophan at this site, which is located adjacent to a conserved Zn binding site, creates an unstable Zn-deficient protein that loses its ability to efficiently activate Sod1. Intriguingly, R₁₆₃W Ccs can reduce copper (i.e., Cu(II) → Cu(I)) bound in its Sod1-like domain (D2), and this novel redox event is a

SUBMITTER: Zhang B 

PROVIDER: S-EPMC11722504 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature