Pj. Corringer et al., IDENTIFICATION OF A NEW COMPONENT OF THE AGONIST BINDING-SITE OF THE NICOTINIC ALPHA-7 HOMOOLIGOMERIC RECEPTOR, The Journal of biological chemistry, 270(20), 1995, pp. 11749-11752
Tryptophan 54 of the alpha 7 neuronal nicotinic homooligomeric recepto
r is homologous to gamma-Trp-55 and delta-Trp-57 of non-alpha subunits
of Torpedo receptor labeled by d-tubocurarine. This residue was mutat
ed on the alpha 7-V201-5-hydrorrytryptamine (5HT)(3) homooligomeric ch
imera, which displays alpha 7 nicotinic pharmacology, and for which bo
th equilibrium binding studies and electro physiological recordings co
uld be carried out in parallel. Replacement of Trp-54 by a Phe, Ala, o
r His causes a progressive decrease both in binding affinity and in re
sponses (EC(50) or IC50) for acetylcholine, nicotine, and dihydro-beta
-erythroidine, without significant modification in alpha-Bgtx binding.
Except for Gln-56, comparatively small effects are observed when the
other residues of the 52-58 region are mutated into alanine. These dat
a support the participation of Trp-54 to ligand binding, and provide e
vidence for a new ''complementary component'' of the alpha 7 nicotinic
binding site, distinct from its three-loop ''principal component,'' a
nd homologous to the ''non-alpha component'' present on gamma and delt
a subunits.