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.