Modulation of the neurotensin solution structure in the presence of ganglioside GM1 bicelle

Neurotensin (NT) is an endogenous tridecapeptide neurotransmitter that shows multiple biological function in central and peripheral nervous systems. Gangliosides are glycosphingolipids, most abundant in the plasma membrane of nerve cells. Here we investigate the change of neurotensin solution structure induced by isotropic CHAPS-PC bicelles with and without ganglioside GM1 using solution state NMR spectroscopy. In aqueous solution the peptide is predominately unstructured. In the presence of bicelle overall structure of the peptide is stabilized. In CHAPS-PC bicelle neurotensin adopts 310 helical structure. In the presence of GM1 containing bicelle, the peptide adopts predominately 310 helical structures with small amount of α-helical structure. These results are consistent with the CD spectroscopic results. Neurotensin interacts better with GM1 containing bicelle than that of the CHAPS-PC bicelle. Docking studies between the Neurotensin Receptor3 (NTS3) and different NT conformations also indicated better binding of the NT conformation obtained in presence of GM1-containing bicelles.

Highlights► NT is predominantly unstructured in aqueous solution. ► In the presence of PC bicelle NT adopts 310 helical structure. ► In GM1 bicelle NT adopts predominating 310 helical structure. ► Small fraction of α-helical structure also acquired in GM1 bicelle. ► NT interacts strongly with GM1 bicelle than that of the PC bicelle.