A stereochemical test of a proposed structural feature of the nicotinic acetylcholine receptor.
Understanding the gating mechanism of the nicotinic acetylcholine receptor (nAChR) and similar channels constitutes a significant challenge in chemical neurobiology. In the present work, we use a stereochemical probe to evaluate a proposed pin-into-hydrophobic socket mechanism for the alphaVal46 side chain of the nAChR. Utilizing nonsense suppression methodology we incorporated isoleucine (Ile), O-methyl threonine (Omt) and threonine (Thr) as well as their side chain epimers (the allo counterparts). Surprisingly, our results indicate that only the pro-S methyl group of the alphaVal46 side chain is sensitive to changes in hydrophobicity, consistent with the precise geometrical requirements of the pin-into-socket mechanism.
Hanek
Ariele P
AP
Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Lester
Henry A
HA
Dougherty
Dennis A
DA
D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
D021122:Protein Subunits; D011978:Receptors, Nicotinic