Allosteric mechanism in AMPA receptors: a FRET-based investigation of conformational changes.

ABSTRACT: Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the primary mediators of fast excitatory synaptic transmission in the mammalian CNS. Structures of the extracellular ligand-binding domain suggest that the extent of cleft closure in the ligand-binding domain controls the extent of activation of the receptor. Here we have developed a fluorescence resonance energy transfer-based probe that allows us to study the extent of cleft closure in the isolated ligand-binding domain in solution. These investigations show that the wild-type protein exhibits a graded cleft closure that correlates to the extent of activation, which is in qualitative agreement with the crystal structures. However, the changes in extent of cleft closure between the apo and agonist-bound states a

SUBMITTER: Ramanoudjame G 

PROVIDER: S-EPMC1502482 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature