Ecdysis triggering hormone peptide in the African malaria mosquito Anopheles gambiae:The peptide structure for receptor activation
摘要Infections by mosquito-borne diseases represent one of the leading causes of death in third world countries.The rapid progression of resistance to conven-tional insecticide causes a significant threat to the highly efficient preventive meth-ods currently in place.Insect neuropeptidergic system offers potential targets to con-trol the insect vectors.The essential roles of the neuropeptide ecdysis triggering hor-mone(ETH)in insect development and reproduction led us to attempt understanding of the fundamentals of the biochemical interaction between ETH and its receptor in the African malaria mosquito Anopheles gambiae.One of two ETH peptides of the African malaria mosquito(AgETH1),a small peptide hormone with 17 amino acid residues(SESPGFFIKLSKSVPRI-NH2),was studied to elucidate its molecular structure.N-termini deletions and mutations of conserved amino acids in the ligand revealed the critical residues for the receptor activation.The solution structure of AgETH1 using 2D 1H-1H nuclear magnetic resonance(NMR)spectroscopy and nuclear overhauser effect(NOE)derived constraints revealed a short alpha helix between residues 3S and 1 1S.The NMR solution structure of AgETH1 will be of significant assistance for designing a new class of insecticidal compounds that acts on the AgETH receptor aiming for in silico dock-ing studies.
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