Active conformation of an insect neuropeptide family.
To understand the structural and chemical basis for insect neuropeptide activity, we have designed, synthesized, and determined the conformation of a biologically active cyclic analog of the pyrokinins, an insect neuropeptide family that mediates myotropic (visceral muscle contractile) activity. Members of this insect neuropeptide family share the common C-terminal pentapeptide sequence Phe-Xaa-Pro-Arg-Leu-NH2 (Xaa = Ser, Thr, or Val). Circular dichroic, nuclear magnetic resonance, and molecular dynamics analyses of the conformationally restricted cyclic pyrokinin analog cyclo(-Asn-Thr-Ser-Phe-Thr-Pro-Arg-Leu-) indicated the presence of a beta-turn in the active core region encompassing residues Thr-Pro-Arg-Leu. The rigid cyclic analog retains biological activity, suggesting that its C-terminal beta-turn is the active pyrokinin conformation recognized by the myotropic receptor. As individual pyrokinins and pyrokinin-like neuropeptides demonstrate both oviduct-contractile and pheromone-biosynthesis activities in various insects, the biologically active beta-turn structure reported here holds broad significance for many biological processes.
Nachman
R J
RJ
Veterinary Toxicology and Entomology Research Laboratory, U.S. Department of Agriculture, College Station, TX 77840.
Roberts
V A
VA
Dyson
H J
HJ
Holman
G M
GM
Tainer
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003058:Cockroaches / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009479:Neuropeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation
D009479:Neuropeptides; D010456:Peptides, Cyclic; C068869:cyclo(asparaginyl-threonyl-seryl-phenylalanyl-threonyl-prolyl-arginyl-leucyl)