Prediction of the secondary structure of the nicotinic acetylcholine receptor nontransmembrane regions.
A consensus prediction for the secondary structure of the muscle nicotinic acetylcholine receptor (alpha, beta, gamma, and delta subunits) extracellular regions is presented. This protein is a member of the ligand-gated ion channel superfamily, which also encompasses the 5HT3, GABAA, and glycine receptors. The strategy used here is based on the application of six different prediction methods to an alignment of 118 sequences of this superfamily. A consensus prediction was finally produced for each of the four different subunits of the muscle nicotinic receptor nonmembrane regions. The predicted percentages, with respect to the total receptor length, and averaged for the four subunits are as follows: alpha-helix 29.7%, beta-sheet 24.9%, and turn + coil 21.7%. When adding to these values the estimations of the secondary structure reported for the transmembrane region only, the results are in agreement with those obtained experimentally by Yager et al. and Méthot et al. The deviations with respect to these experimental estimations are alpha-helix +2.8%, beta-sheet -4/-5% and turn + coil +3/+2%, respectively. Considering the predictions made for individual subunits, the best approximation was obtained for the alpha subunit, with deviations of -0.2% for alpha-helix, -2.5/-1.5% for beta-sheet, and +0.9/+1.9% for turn + coil. The prediction was used to infer the residues involved in forming three helices that presumably flank the ligand-binding pocket and to propose mechanism for transferring the information of the ligand binding to the ion channel.
Ortells
M O
MO
Instituto de Neurociencia (CONICET), Facultad de Ciencias Exactas y Naturales, Depto. Cs. Biológicas, Universidad de Buenos Aires, Argentina. mortells@mail.retina.ar
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011978:Receptors, Nicotinic / Q000737:chemistry*
D011978:Receptors, Nicotinic