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 alpha-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.

The granin family of uniquely acidic proteins of the diffuse neuroendocrine system: comparative and functional aspects

“…Its primary sequence indicates an acidic peptide with four net negative charges (Fischer-Colbrie, Laslop & Kirchmair, 1995) and two a-helices (Oulyadi, Davoust & Vaudry, 1997). Immunoreactive SN is widely distributed (Kirchmair et al, , 1994, overlapping partly but not completely with established neurotransmitter and neuropeptide systems (Marksteiner et al, 1993).…”

Secretoneurin: A New Player in Angiogenesis and Chemotaxis Linking Nerves, Blood Vessels and the Immune System

“…The secondary structure of the peptide was investigated by two-dimensional 1 H-NMR, CD spectroscopy and molecular modeling [8]. The conformation of SN is composed of two highly ordered α-helices ranging from residues 3-8 (EIVEEQ) and [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Molecular Cloning, Mapping, and Polymorphism of the Porcine SCG2 gene

“…The sequences of these two peptides have been remarkably well preserved during evolution (Anouar et al 1996;Turquier et al 2000), suggesting that they subserve important functions. SN was first characterized in frog (Vaudry and Conlon 1991), and its 3D structure has been characterized (Oulyadi et al 1997). It has been shown to exert various biological activities, such as modulation of the inflammatory response (Wiedermann 2000) and stimulation of neuronal activity (Agneter et al 1995;Gasser et al 2003).…”