Mapping the Conformational Landscape of Glutamate Receptors Using Single Molecule FRET

The ionotropic glutamate receptors mediate excitatory neurotransmission in the mammalian central nervous system. These receptors provide a range of temporally diverse signals which stem from subunit composition and also from the inherent ability of each member to occupy multiple functional states, the distribution of which can be altered by small molecule modulators and binding partners. Henceit becomesessential to characterize the conformationallandscapeof the receptors under this variety of different conditions. This has recently become possible due to single molecule fluorescence resonance energy transfer measurements, along with the rich foundation of existing structures allowing for direct correlations between conformational and functional diversity.