Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes.

ABSTRACT: Sequence evolution of protein complexes (PCs) is constrained by protein-protein interactions (PPIs). PPI-interfaces are predominantly conserved and hotspots for disease-related mutations. How do lipid-protein interactions (LPIs) constrain sequence evolution of membrane-PCs? We explore Respiratory Complexes (RCs) as a case study as these allow to compare sequence evolution in subunits exposed to both lipids in inner-mitochondrial membrane (IMM) and lipid-free aqueous matrix. We find that lipid-exposed surfaces of the IMM-subunits but not of the matrix subunits are populated with non-PPI disease-causing mutations signifying LPIs in stabilizing RCs. Further, IMM-subunits including their exposed surfaces show high intra-kingdom sequence conservation but remarkably diverge beyond. Molecular Dyn

SUBMITTER: Gupta P 

PROVIDER: S-EPMC11868549 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature