Interaction of tachykinins with phospholipid membranes: A neutron diffraction study

Tachykinins are a group of peptides which bind to G-protein-coupled receptors. Receptor affinity appears to depend on different secondary structures of tachykinin which share the same Hydrophobic carboxy-terminal sequence, FXGLM. Receptor activation is thought to be due to the carboxy-terminal submerging into the bilayer and the amino-terminal binding on the surface. Binding of tachykinins to phospholipid bilayers may take place both on the aqueous membrane surface and in the hydrophobic region. The two-state equilibrium appears to depend on the surface charge of the membrane. Deuterating substance P and neurokinin A at their carboxy-terminals, our results show two populations of label for each peptide. One is very close to the water-hydrocarbon interface, the other some 13 Å deeper. We report that the bilayer location of the two tachykinins is remarkably similar, thereby inferring that receptor specificity must be controlled by finer levels of structure.