TY - JOUR
T1 - Elucidating the Molecular interaction of Zebrafish (Danio rerio) Peptidoglycan recognition protein 2 with Diaminopimelic acid and Lysine type Peptidoglycans using in-silico Approaches
AU - Rout, Ajaya Kumar
AU - Paramanik, Sunanda
AU - Dehury, Budheswar
AU - Acharya, Varsha
AU - Swain, Himanshu Sekhar
AU - Pradhan, Sukanta Kumar
AU - Behera, Bhaskar
AU - Pati, Soumen Kumar
AU - Behera, Bijay Kumar
AU - Das, Basanta Kumar
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Innate immunity
KW - Zebrafish
KW - PGRP 2
KW - Molecular dynamics simulation
KW - Principal component analysis
U2 - 10.1080/07391102.2019.1666742
DO - 10.1080/07391102.2019.1666742
M3 - Journal article
C2 - 31517586
SN - 0739-1102
VL - 38
SP - 3687
EP - 3699
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 12
ER -