Solution conformation of non-mammalian tachykinin physalaemin in lipid micelles by nuclear magnetic resonance

Physalaemin (PHY), a non-mammalian tachykinin, binds selectively to neurokinin-1 (NK1) receptor with high affinity. Both the aqueous and lipid-induced conformations of PHY have been studied using two-dimensional nuclear magnetic resonance techniques. These data show that in water PHY prefers to be in an extended conformation and that in the presence of perdeuterated dodecylphosphocholine micelles, a membrane model system, a helical conformation is observed from Pro4 to the C-terminus. Comparison of the structures ofPHYand other NK ligands along with structure activity studies reported on these peptide ligands suggests that helical backbone structural motif is necessary for the binding of these NK ligands to the various NK receptors. Furthermore, consensus in the structures of these ligands suggests that these ligands must be binding along the highly hydrophobic face of the helix that contains the important hydrophobic residues, Phe7, Leu10, and Met11, that are highly conserved in most of the ligands.