Subunit interfaces contribute differently to activation and allosteric modulation of neuronal nicotinic acetylcholine receptors.

ABSTRACT: Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the nervous system and are implicated in many normal and pathological processes. The structural determinants of allostery in nAChRs are not well understood. One class of nAChR allosteric modulators, including the small molecule morantel (Mor), acts from a site that is structurally homologous to the canonical agonist site but exists in the β(+)/α(-) subunit interface. We hypothesized that all nAChR subunits move with respect to each other during channel activation and allosteric modulation. We therefore studied five pairs of residues predicted to span the interfaces of α3β2 receptors, one at the agonist interface and four at the modulator interface. Substituting cysteines in these positions, we used disulfide trap

SUBMITTER: Short CA 

PROVIDER: S-EPMC4332533 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature