Crystal and solution structures of a novel antimicrobial peptide from Chrysomya megacephala

Antimicrobial peptides (AMPs) are small amphipathic peptides that exhibit bactericidal activity against a wide range of pathogenic microorganisms and are considered to be potential substitutes for antibiotics effective against microbial infection. PSK, an 84‐amino‐acid AMP recently isolated from Chrysomya megacephala larvae, probably belongs to the mitochondrial ATPase inhibitor family according to its sequence. No member of this family from an insect has been structurally characterized to date. In this study, the crystal structure of full‐length PSK determined by molecular replacement using an ab initio modeled ensemble as a search model and a solution structure obtained from small‐angle X‐ray scattering (SAXS) measurements are reported. The crystal structure reveals a distinct fold compared with those of homologous peptides, in that PSK comprises two antiparallel α‐helices rather than a single long helix, which is in good agreement with the SAXS‐based ab initio model. However, the peptide exists as a monomer in solution, even though a stable dimer was observed in the crystal structure. This apparent contradiction may reflect different oligomerization states that may be implicated in its bioactivity. The data presented here have established a solid basis for further mechanistic studies of this novel insect AMP. The structure of PSK, a novel antimicrobial peptide identified in Chrysomya megacephala larvae, was determined by X‐ray crystallography and small‐angle X‐ray scattering, which revealed a distinct fold compared with published homologous peptides.