Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

65-POS Board 65 Submillisecond Dynamics and Activation State of the Ligand-binding Domain of the

NMDA Receptor Hugo Sanabria . n/a, Clemson, USA.

N-methyl-D-aspartate (NMDA) receptors belong to the ionotropic glutamate receptor family. However, in comparison to other glutamic receptors, channel gating in NMDA receptors is regulated by the binding of glutamate to the glutamate-binding domain at the GluN2A subunit and glycine to the glycine-binding domain of the GluN1 subunit. Of particular interest, we are set to study the partial agonism of the GluN1 ligand binding domain (LBD). Numerous glutamate receptors have revealed that the LBD closure mechanism relates to the level of agonism, where a full agonist closes the bilobed clamshell cleft of the LBD, whereas a full antagonist opens fully the cleft. Using smFRET and multiparameter fluorescence detection, we revealed the existence of a new conformational state, most likely responsible to initiate channel activation. Two additional conformations are identified, where both are consistent with crystallographic structures. Moreover, we probe the submillisecond dynamics by time-window analysis and we monitor the dynamic equilibrium between the identified conformational states.

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