Dynamics of cleft closure of the GluA2 ligand-binding domain in the presence of full and partial agonists revealed by hydrogen-deuterium exchange.

ABSTRACT: The majority of excitatory neurotransmission in the CNS is mediated by tetrameric AMPA receptors. Channel activation begins with a series of interactions with an agonist that binds to the cleft between the two lobes of the ligand-binding domain of each subunit. Binding leads to a series of conformational transitions, including the closure of the two lobes of the binding domain around the ligand, culminating in ion channel opening. Although a great deal has been learned from crystal structures, determining the molecular details of channel activation, deactivation, and desensitization requires measures of dynamics and stabilities of hydrogen bonds that stabilize cleft closure. The use of hydrogen-deuterium exchange at low pH provides a measure of the variation of stability of specific hydrog

SUBMITTER: Ahmed AH 

PROVIDER: S-EPMC3779761 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature