Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors.

ABSTRACT: AMPA receptors (AMPARs) are tetrameric ligand-gated ion channels that couple the energy of glutamate binding to the opening of a transmembrane channel. Crystallographic and electrophysiological analysis of AMPARs has suggested a coupling between (1) cleft closure in the bilobate ligand-binding domain (LBD), (2) the resulting separation of transmembrane helix attachment points across subunit dimers, and (3) agonist efficacy. In general, more efficacious agonists induce greater degrees of cleft closure and transmembrane separation than partial agonists. Several apparent violations of the cleft-closure/efficacy paradigm have emerged, although in all cases, intradimer separation remains as the driving force for channel opening. Here, we examine the structural basis of partial agonism in GluA4

SUBMITTER: Birdsey-Benson A 

PROVIDER: S-EPMC2844711 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature