Co-evolution of alpha-helical transmembrane protein residues: large-scale variant profiling and complete mutational landscape of 2277 known PDB entries representing 504 unique human protein sequences.

ABSTRACT: Membrane proteins play fundamental roles in cellular function, yet the evolutionary dynamics of their amino acid composition remain poorly understood. Our current study investigates the substitutional landscape and evolutionary patterns of hydrophilic and hydrophobic residues in membrane α-helical proteins, addressing a significant gap in our knowledge of protein evolution. We analyzed 2277 high-resolution protein structures from the RCSB Protein Data Bank corresponding to 458 unique PDB structures, 504 UniProt transmembrane entries and their AlphaMissense predicted mutational libraries including more than 5.8 million amino acid substitutions, focusing on known transmembrane α-helical proteins in Homo sapiens. Our analysis showed that the pathological outcome of the substitutions is divers

SUBMITTER: Karagol T 

PROVIDER: S-EPMC12579659 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature