Mechanism of AMPA receptor activation by partial agonists: disulfide trapping of closed lobe conformations.

ABSTRACT: The mechanism by which agonist binding to an ionotropic glutamate receptor leads to channel opening is a central issue in molecular neurobiology. Partial agonists are useful tools for studying the activation mechanism because they produce full channel activation with lower probability than full agonists. Structural transitions that determine the efficacy of partial agonists can provide information on the trigger that begins the channel-opening process. The ligand-binding domain of AMPA receptors is a bilobed structure, and the closure of the lobes is associated with channel activation. One possibility is that partial agonists sterically block full lobe closure but that partial degrees of closure trigger the channel with a lower probability. Alternatively, full lobe closure may be required

SUBMITTER: Ahmed AH 

PROVIDER: S-EPMC3186401 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature