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 channel-lining M2 segments of the nicotinic acetylcholine receptor (AChR) and of a glutamate receptor of the NMDA subtype (NMDAR) were determined using solution NMR experiments on micelle samples, and solid-state NMR experiments on bilayer samples. Both M2 segments form straight transmembrane alpha-helices with no kinks. The AChR M2 peptide inserts in the lipid bilayer at an angle of 12 degrees relative to the bilayer normal, with a rotation about the helix long axis such that the polar residues face the N-terminal side of the membrane, which is assigned to be intracellular. A model built from these solid-state NMR data, and assuming a symmetric pentameric arrangement of M2 helices, results in a funnel-like architecture for the channel, with the wide opening on the N-terminal intracellular side.
Opella
S J
SJ
Department of Chemistry, University of Pennsylvania, Philadelphia 19014, USA. opella@chestnut.chem.upenn.edu
Marassi
F M
FM
Gesell
J J
JJ
Valente
A P
AP
Kim
Y
Y
Oblatt-Montal
M
M
Montal
M
M
D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000235:genetics; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D007553:Isotope Labeling; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012996:Solutions
D007473:Ion Channels; D008051:Lipid Bilayers; D008055:Lipids; D008823:Micelles; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D012996:Solutions