Structure of prejunctional receptor binding analog of human neuropeptide Y dimer ANA-NPY.

Human neuropeptide Y (NPY) analog ANA-NPY or [L17, Q19, A20, A23, L28, L31]NPY (13-36)-amide binds weakly to postjunctional receptors to raise blood pressure but binds tightly to prejunctional receptors to inhibit neurotransmitter release. ANA-NPY forms a well-conserved anti-parallel helical structure overlapping E23-Y36 with strong amphipathic character. The C-terminal portions of the monomers are better defined than the N-terminal ends. The N-terminal helices extend only from D16-E23/L24. The prejunctional receptor-specific binding site is confined within the C-terminal helices while the residues responsible for partial binding to the postjunctional receptors are located in the more disordered N-terminal segments.