An extensive and diverse gene family of nicotinic acetylcholine receptor alpha subunits in Caenorhabditis elegans

Using reverse transcription-polymerase chain reactions the transcription of eight novel candidate nicotinic acetylcholine receptor (nAChR) a subunit g enes has been demonstrated in the nematode Caenorhabditis elegans. Together with five other ct subunit genes described elsewhere by ourselves (unc-38) and other workers (deg-3, acr-4, Ce21 and nci 6), this is now the largest known family of nAChR a subunit genes in a single species. By homology we h ave identified four groups of cu subunits, DEG-3-like; ACR-16[Ce21]-like; U NC-38-like and ACR-8-like, Five C, elegans nAChR a subunits contain a modif ication in loop C of the ACh binding site in which the normally conserved T yr-x-Cys-Cys, is replaced by a distinct motif (Tyr-x-x-Cys-Cys). Variation is also found in the channel lining M2 regions, including the replacement i n four subunits of the highly conserved leucine at the 9' position by valin e and most notably, the replacement in all ACR-S-like subunits of the highl y conserved glutamic acid at the -1' position by histidine. Restrained mole cular dynamics simulations have been used to generate homo-pentameric M2 he lix bundle models for ct subunits and possible functional implications exam ined, The calculated electrostatic potential energy profile for the M2 regi on of ACR-S differs strikingly from that of ACR-16[Ce21] largely due to the presence of histidine at the -1' position, suggesting a possible perturbat ion of nAChR channel action permeability in the presence of this subunit ty pe.