PREDICTION OF THE SECONDARY STRUCTURE OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR NONTRANSMEMBRANE REGIONS

A consensus prediction for the secondary structure of the muscle nicot inic acetylcholine receptor (alpha, beta, gamma, and delta subunits) e xtracellular regions is presented, This protein is a member of the lig and-gated ion channel superfamily, which also encompasses the 5HT(3), GABA(A), and glycine receptors, The strategy used here is based on the application of six different prediction methods to an alignment of 11 8 sequences of this superfamily, A consensus prediction was finally pr oduced 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 agreem ent with those obtained experimentally by Yager et al.(1) and Methot e t al.(2) The deviations with respect to these experimental estimations are a-helix +2.8%, beta-sheet -4/-5% and turn+coil +3/+2%, respective ly. Considering the predictions made for individual subunits, the best approximation was obtained for the a subunit, with deviations of -0.2 % for alpha-helix, -2.5/-1.5% for beta-sheet, and +0.9/+1.9% for turncoil. The prediction was used to infer the residues involved in formin g three helices that presumably flank the ligand-binding pocket and to propose mechanism for transferring-the information of the ligand bind ing to the ion channel. (C) 1997 Wiley-Liss, Inc.