A determination of the solution conformation of secretoneurin, a neuropeptide originating from the processing of secretogranin II, by 1H-NMR and restrained molecular dynamics

Abstract

Secretoneurin is a 33-amino-acid polypeptide generated by proteolytic cleavage of secretogranin II at paired dibasic sequences. It has recently been shown that secretoneurin exerts biological activities such as stimulation of dopamine release from striatal neurons and activation of monocyte migration, suggesting that the peptide may modulate both neurotransmission and inflammatory response. In the present study, we have investigated the conformation of synthetic secretoneurin in methanol solution by two-dimensional 1H-NMR, circular dichroism and molecular modeling. Using sequential information, specific assignments have been made for resonances arising from all protons, except for the labile proton of the N-terminal Thr of the peptide. The solution structure of secretoneurin has been determined by distance geometry and restrained molecular dynamics, using distance and dihedral constraints derived from the NMR data. The conformation obtained is composed of two contiguous α-helices comprising residues Glu3-Gln8 and Pro11-Gly25. An excellent concordance was observed between these conformational data and prediction with the AGADIR program for the location for the helices in the sequence. These conformational data should help to elucidate the involvement of the tertiary interactions and to design secretoneurin analogs.