C-TERMINAL CLAW STABILISATION IN CORVUS AVIAN BETA DEFENSIN 7 AND ITS MUTATION STUDIES

Antimicrobial peptides are considered as promising and potential next-generation antibiotics on account of their broad spectrum of antimicrobial activity and unique mode of microbial killing. For therapeutic application, it is essential to consider the hemolytic or cytotoxic property of AMPs along with antimicrobial function. In the current study, an avian beta-defensin 7 (AvBD7) gene was identified from Corvus splendens. The predicted amino acid sequence showed the presence of β defensin core motif and three disulphide bridges. We analysed the interaction of wild and mutant analogues of mature Corvus AvBD7 dimer with neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) that mimics mammalian membranes using molecular dynamics simulation studies. Hydrophobic residues at the N-terminus of each monomer were found to provide stability in the dimeric form. In both monomer and dimer, Asp3 and Asp4 interact with Tyr40 and Ser41 thereby helping in maintaining a claw shape at the C-terminus. During simulation, we found that the C-terminus claw region of wild dimer remained intact than its mutant analogs, and also wild AvBD7 exhibited a greater propensity to bind POPC membrane than its mutant analogs. Based on the membrane-peptide distance and number of hydrogen bonds formed between peptide and membrane, we conclude that the alanine mutant might be least hemolytic as it showed reduced propensity to bind to POPC membrane.