Understanding metal binding in neuromedin C

Abstract

Neuromedin C (NMC) is an endogenous bombesine-like peptide that is present mainly in the central nervous system (CNS) and the gastrointestinal tract. In addition to its biological function as a neuropeptide, NMC acts as a growth factor for some tumours and plays a major role in transition metal homeostasis in the CNS. In this work, we determined the binding constants and main thermodynamic parameters for the complexes of NMC with Cu2+, Ni2+ and Co2+ ions. The binding constants obtained were consistent with the Irving–Williams series, where the affinity for transition metal cations increases across the periodic table. All NMC complexes had a positive enthalpy (ΔH > 0), which is consistent with an entropy-driven process. The affinity of NMC for Cu2+ and Ni2+ was similar to that of other peptides also containing the ATCUN motif. However, the low concentrations of NMC in serum suggest that the peptide is unlikely to play a biological role in metal homeostasis in the CNS or the gastrointestinal tract.