Structural and dynamic studies of the γ-M4 trans-membrane domain of the nicotinic acetylcholine receptor

Abstract

A structural characterization of a synthetic peptide corresponding to the fourth transmembrane domain (M4-TMD) of the γ-subunit of the nicotinic acetylcholine receptor from Torpedo californica has been undertaken. Solid-state NMR and CD spectroscopy studies indicate that upon reconstitution into lipid vesicles or magnetically aligned lipid bilayers, the synthetic M4-TMD adopts a linear α-helical conformation with the helix aligned within 15° of the membrane normal. Furthermore, analysis of the motional averaging of anisotropic interactions present in the solid-state NMR spectra of the reconstituted peptide, indicate that the dynamics of the peptide within the bilayer are highly sensitive to the phase adopted by the lipid bilayer, providing an insight into how the interaction of lipids with this domain may play a important role in the modulation of this receptor by its lipid environment.

• Nicotinic acetylcholine receptor
• magnetically aligned phases
• ether-linked bicelles
• cross-polarization magic-angle spinning solid-state NMR