Sequence/structural/functional relationships between Ganoderma fungal immunomodulatory proteins (gFIPs) and proteins involved in the modulation of immune response

Fungal Immunomodulatory Proteins from Ganoderma species (gFIPs) have garnered significant interest due to their potential therapeutic applications in modulating immune responses. This study investigates the sequence, structural, and functional relationships of gFIPs with other proteins involved in immune modulation. Utilizing molecular modelling, multiple sequence alignments, and structural superimposition, we analysed two FIP crystallized structures (PDB IDs: 3F3H and 3KCW) alongside homologous sequences from various taxonomic groups. Our results reveal conserved motifs across fungal, bacterial, and human sequences, indicating potential functional similarities. Comparative structural analysis highlights significant conservation in FIP architecture, with variations primarily in the N-terminal regions. Notably, structural alignment with bacterial toxins, such as ADP-ribosylating binary toxin from Clostridium difficile or protective antigen of Anthrax toxin from Bacillus anthracis suggests mechanistic insights into FIP's immunomodulatory actions. Structural similarities between gFIPs and immune-related proteins, such as bacterial toxin-binding domains, antibody fragments, T-cell receptor components, and immune checkpoint regulators (PD-1) suggest their potential involvement in immune response/inflammation signalling pathways. This comprehensive analysis elucidates the structural basis for the diverse biological activities of gFIPs and underscores their potential as therapeutic agents in immune-related diseases.