Literature review reveals diverse functional roles of START domain proteins beyond lipid transport in bacteria, highlighting their potential as antimicrobial drug targets.
Key Points
To synthesize structural and functional knowledge regarding bacterial StAR-related lipid-transfer (START) domain proteins and identify existing knowledge gaps.
Reviewed and integrated experimental, structural, and evolutionary literature on bacterial START domain proteins across diverse taxa.
Conducted an in-depth evaluation of START domain functions in the phylum Actinomycetota, focusing particularly on Mycobacterium tuberculosis.
Bacterial START domains preserve the core helix-grip fold for hydrophobic ligand binding but are generally smaller and less conformationally flexible than eukaryotic counterparts.
Unlike mammalian START domains that specialize in lipid transport and signaling, bacterial variants participate in small-molecule binding, metabolic regulation, enzymatic catalysis, and stress adaptation.
START domain proteins are uniquely prevalent in Actinomycetota, with specific proteins in M. tuberculosis emerging as candidate therapeutic targets.