Proximal relationships of moonlighting proteins in Escherichia coli: A mathematical genomics perspective

Moonlighting proteins in Escherichia coli (E.coli) perform multiple independent functions without altering their primary amino acid sequence, challenging the "one gene-one enzyme" hypothesis. Bacterial proteins serve various functions, including host cell adhesion, extracellular matrix interaction, and immune modulation, while also supporting essential physiological processes within the bacteria. Identifying these proteins in pathogens and tracking their genetic changes is crucial for understanding bacterial survival and virulence. A quantitative understanding of these proteins is pivotal as it enables the identification of specific patterns and relationships between amino acid composition, protein stability, and functional versatility. This study quantitatively analyzes 50 E. coli moonlighting proteins, revealing alanine as the most frequent residue (8.92 % median), while cysteine had the lowest (0.58 %). A preference for non-polar residues was observed (polar-to-non-polar ratio: 0.89). Quantitative features analyses identified seven distinct proximal sets, reflecting the pro- teins' spatial arrangements of amino acids, structural diversity, and functional roles in processes such as metabolism, stress response, and gene regulation. The highest percentage of disordered residues was 56.45 %, significantly lower than 100 % in human moonlighting proteins. These results deepen our understanding of the multifunctionality of E. coli moonlighting proteins, indicating their adaptability and implications for bacterial survival and pathogenicity.