Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Escherichia coli / genetics
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Ion Channel Gating
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Ion Channels / chemistry*
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Isotope Labeling
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Lipid Bilayers
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Lipids / chemistry
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Magnetic Resonance Spectroscopy / methods
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Micelles
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Models, Chemical
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Models, Molecular
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Molecular Sequence Data
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Peptide Fragments / chemistry*
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Conformation
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Receptors, N-Methyl-D-Aspartate / chemistry*
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / metabolism
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Receptors, Nicotinic / chemistry*
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Receptors, Nicotinic / genetics
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Receptors, Nicotinic / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Solutions
Substances
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Ion Channels
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Lipid Bilayers
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Lipids
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Micelles
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Peptide Fragments
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Receptors, N-Methyl-D-Aspartate
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Receptors, Nicotinic
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Recombinant Proteins
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Solutions
Associated data
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PDB/1A11
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PDB/1CEK
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PDB/2NR1