Moonlighting Proteins: Some Hypotheses on the Structural Origin of Their Multifunctionality.

ABSTRACT: Moonlighting proteins-single polypeptides performing multiple, often unrelated functions-are increasingly recognized as key players in human disease and microbial pathogenesis, making their identification crucial for understanding disease mechanisms and developing targeted therapies. This study addresses the unresolved question of how such multifunctionality evolves, focusing on two potential structural mechanisms: Non-Orthologous Gene Displacement/Non-Homologous Isofunctional Enzymes (NOGD/NHIE), where evolutionarily unrelated proteins perform the same function, and Fold-Switching Proteins (FSP), which adopt alternative secondary structures to switch functions without sequence changes. We analyzed the overlap between known human moonlighting proteins (from MultitaskProtDB-II) and curated

SUBMITTER: Cedano J 

PROVIDER: S-EPMC12607968 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature