title: A mixed helix-beta-sheet model of the transmembrane region of the nicotinic acetylcholine receptor.
abstract: We have modelled the transmembrane region of the alpha 7 nicotinic acetylcholine receptor as a mixed alpha-helical/beta-sheet structure. The model was mainly based on the crystal structure of a pore-forming toxin, heat-labile enterotoxin. This is a pentameric protein having a central pore or channel composed of five alpha-helices, one from each of the 5 B subunits that form this pentamer. The remainder of this structure is beta-sheet, loops and a short alpha-helix, not included in the model. The model uses this channel as a template to build the transmembrane region, from M1 to the middle of M3. The remainder of M3 and M4 were built de novo as alpha-helices. Great consideration was given to labelling data available for the transmembrane region. In general terms, the shape of the model agrees very well with that obtained independently by electron microscopic analysis and the secondary structure predicted by the model is in accord with that estimated independently by Fourier transform infrared spectroscopy. The M2 helical region of the model is only slightly kinked, contrary to what is inferred from electron microscopic analysis, but has the same overall shape and form. On the membrane face of the model, the presence of deep pockets may provide the structural basis for the distinction between annular and non-annular lipid binding sites. Also, the transmembrane region is clearly asymmetric in the direction perpendicular to the membrane, and this may have strong influence on the surrounding lipid composition of each leaflet of the cytoplasmic membrane.
authors.affiliation: School of Biology and Biochemistry, University of Bath, UK.
authors.forename: M O
authors.initials: MO
authors.lastname: Ortells
authors.forename: G G
authors.initials: GG
authors.lastname: Lunt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001427:Bacterial Toxins / Q000737:chemistry; D002645:Chickens; D004768:Enterotoxins / Q000737:chemistry; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D007473:Ion Channels / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry*; D016415:Sequence Alignment; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007473:Ion Channels; D008055:Lipids; D011978:Receptors, Nicotinic; C027538:heat-labile enterotoxin, E coli