Aspects of the molecular structure and dynamics of neuropeptide Y

Human neuropeptide Y (hNPY) and the Q34-->P34 mutant (P34-hNPY) have been c haracterized by CD spectroscopy. hNPY self-associates in aqueous solution w ith a dimerization constant in the micromolar range. The self-association c orrelates with an increase in secondary-structure content which was studied as a function of concentration, temperature and pH. The effects of tempera ture were measured in water (5-84 degrees C) and in ethanediol/ water (2 : 1) (-90 degrees to +90 degrees C). A single-residue mutation, Q34-->P34, af fects the pH, thermal and self-association properties of NPY. The CD result s are correlated with photochemically induced dynamic nuclear polarization NMR experiments which show that the tyrosines at the interface between two monomer units present limited accessibility to a photoreactive dye. An equi librium state is described, involving a PP-fold monomer form and a handshak e dimer form, that accommodates the physicochemical properties of NPY.