F. Kotzyba-hibert et al., Molecular investigations on the nicotinic acetylcholine receptor - Conformational mapping and dynamic exploration using photoaffinity labeling, MOL NEUROB, 20(1), 1999, pp. 45-59
The nicotinic acetylcholine receptor (nAChR) is a well-understood member of
the ligand-gated ion channels superfamily. The members of this signaling p
roteins group, including 5HT(3), GABA(A), glycine, and ionotropic glutamate
receptors, are thought to share common secondary, tertiary, and quaternary
structures on the basis of a very high degree of sequence similarity. Desp
ite the absence of X-ray crystallographic data, considerable progress on st
ructural analysis of nAChR was achieved from biochemical, mutational, and e
lectron microscopy data allowing the emergence of a three-dimensional image
. Photoaffinity labeling and site-directed mutagenesis gave information on
the tertiary structure with respect to the agonist/antagonist binding sites
, the ion channel, and its selectivity filter.
nAChR is an allosterical protein that undergoes interconversion among sever
al conformational states. Time-resolved photolabeling Mras used in an attem
pt to elucidate the structural changes that occur in nAChR on neurotransmit
ter activation. Tertiary and quaternary rearrangements were found in the ch
olinergic binding pocket and in the channel lumen, but the structural deter
minant and the functional link between the binding of agonist and the chann
el gating remain unknown. Time-resolved photolabeling of the functional act
ivated A state using photosensitive agonists might help in understanding th
e dynamic process leading to the interconversion of the different states.