Elucidating the Molecular interaction of Zebrafish (Danio rerio) Peptidoglycan recognition protein 2 with Diaminopimelic acid and Lysine type Peptidoglycans using in-silico Approaches

Peptidoglycan recognition proteins (PGRPs) are the important members of pattern recognition receptors (PRRs) family and represents major constituent of innate immunity. Although PGRPs are structurally conserved through evolution; their involvement in innate immunity are different in vertebrates and invertebrates. They are highly specific for the recognition and in some cases, hydrolyze bacterial peptidoglycans (PGNs). Zebrafish PGRPs (zPGRPs) have both peptidoglycans lytic amidase activity and broad-spectrum bactericidal activity, but far less is known about how these receptors recognize these microbial ligands. Such studies are hindered due to lack of structural and functional configuration of zPGRP. Therefore to fill the research gap, we inferred the three-dimensional architecture of the zPGRP2 through theoretical modeling and investigated the conformational and dynamic properties through molecular dynamics simulations. Docking information of microbial ligands i.e., muramyl pentapeptide-DAP (MPP-Dap), muramyl pentapeptide-LYS (MPP-Lys), muramyl tripeptide-DAP (MTP-Dap), muramyl tripeptide-Lys (MTP-Lys), muramyl tetrapeptide-DAP (MTr-Dap), muramyl tetrapeptide-LYS (MTr-Lys) and tracheal cytotoxin (TCT) in Autodock Vina revealed β1, α2, α4, β4, and loops connecting β1 - α2, α2 - β2, β3 - β4, and α4 - α5 as the key interacting domains participate in ligand recognition. Several conserved amino acids i.e., His31, His32, Ala34, Ile35, Pro36, Lys38, Asp60, Trp61, Trp63, Ala89, His90, Asp106, His143, and Arg144 are predicted to essential for binding and provides stability to these zPGRP-PGN complexes. Our study provides basic molecular information for further research on the immune mechanisms of PGRP's in Zebrafish. The plasticity of the zPGRP's binding site revealed by these microbial ligands suggests an intrinsic capacity of the innate immune system to rapidly evolve specificities to meet new microbial challenges in the future.