Calmodulin Interaction Interface with Plasma Membrane Ca²⁺-ATPase Isoforms: An Integrative Bioinformatic Analysis.

ABSTRACT: Plasma membrane Ca²⁺-ATPases (PMCA) are activated by calmodulin (CaM) via a C-terminal calmodulin-binding domain, CaMBD. Although specific mutations in this domain have been linked to disease, the broader impact of alternative substitutions across the interface remains unexplored. We applied an integrative in silico workflow to test six substitutions within CaMBD positions 1-18, L5R, N6I, I8T, V14E/D, and F18S, across PMCA isoforms 1-4. CaMBD sequences were aligned across isoforms, and candidates for substitutions were selected by conservation and nucleotide feasibility, prioritizing conserved or co-evolutionarily relevant sites, with substitutions possible by single-nucleotide change. PolyPhen-2 screened the impact of the substitutions on the protein functionality, the DisGeNET

SUBMITTER: Martinez-Fresneda M 

PROVIDER: S-EPMC12693652 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature