Mo. Ortells et Gg. Lunt, A MIXED HELIX-BETA-SHEET MODEL OF THE TRANSMEMBRANE REGION OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR, Protein engineering, 9(1), 1996, pp. 51-59
We have modelled the transmembrane region of the alpha 7 nicotinic ace
tylcholine receptor as a mixed alpha-helical/beta-sheet structure, The
model was mainly based on the crystal structure of a pore-forming tox
in, heat-labile enterotoxin. This is a pentameric protein having a cen
tral pore or channel composed of five alpha-helices, one from each of
the 5 B subunits that form this pentamer, The remainder of this struct
ure 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 transmem
brane 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 term
s, the shape of the model agrees very well with that obtained independ
ently by electron microscopic analysis and the secondary structure pre
dicted 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 elect
ron microscopic analysis, but has the same overall shape and form, On
the membrane face of the model, the presence of deep pockets may provi
de the structural basis for the distinction between annular and non-an
nular lipid binding sites, Also, the transmembrane region is clearly a
symmetric in the direction perpendicular to the membrane, and this may
have strong influence on the surrounding lipid composition of each le
aflet of the cytoplasmic membrane.