Structures of the M2 channel-lining segments from nicotinic acetylcholine and NMDA receptors by NMR spectroscopy

The structures of functional peptides corresponding to the predicted channe l-lining M2 segments of the nicotinic acetylcholine receptor (AChR) and of a glutamate receptor of the NMDA subtype (NMDAR) were determined using solu tion NMR experiments on micelle samples, and solid-state NMR experiments on bilayer samples. Both M2 segments form straight transmembrane alpha-helice s with no kinks. The AChR M2 peptide inserts in the lipid bilayer at an ang le of 12 degrees relative to the bilayer normal, with a rotation about the helix long axis such that the polar residues face the M-terminal side of th e membrane, which is assigned to be intracellular. A model built from these solid-state NMR data, and assuming a symmetric pentameric arrangement of M 2 helices, results in a funnel-like architecture for the channel, with the wide opening on the N-terminal intracellular side.