NMDA receptors are ligand-gated ion channels that mediate a number of physiological and pathological phenomena within the mammalian central nervous system. Under the typical course of activation, these receptors bind to glycine and glutamate molecules and undergo a series of conformational changes that results in the opening of a cation-permeable pore in the neuronal plasma membrane. Various aspects of NMDA receptor function are not fully understood, including the phenomenon of negative cooperativity between the glycine- and glutamate-binding sites of the receptor and the mechanism controlling partial agonism. Past studies utilizing static structural snapshots of the receptor or isolated domains of the receptor have provided insufficient insights to fully understand these issues. Herein, I have conducted Förster Resonance Energy Transfer measurements on individual NMDA receptor molecules to observe their conformational landscape under various conditions. These studies have revealed changes in conformation of the receptor that underlie negative cooperativity and partial agonism, thereby affording new insights into the mechanisms controlling these processes.
","abstract_html":"<p>NMDA receptors are ligand-gated ion channels that mediate a number of physiological and pathological phenomena within the mammalian central nervous system. Under the typical course of activation, these receptors bind to glycine and glutamate molecules and undergo a series of conformational changes that results in the opening of a cation-permeable pore in the neuronal plasma membrane. Various aspects of NMDA receptor function are not fully understood, including the phenomenon of negative cooperativity between the glycine- and glutamate-binding sites of the receptor and the mechanism controlling partial agonism. Past studies utilizing static structural snapshots of the receptor or isolated domains of the receptor have provided insufficient insights to fully understand these issues. Herein, I have conducted Förster Resonance Energy Transfer measurements on individual NMDA receptor molecules to observe their conformational landscape under various conditions. These studies have revealed changes in conformation of the receptor that underlie negative cooperativity and partial agonism, thereby affording new insights into the mechanisms controlling these processes.</p>","abstract_has_math":false,"creators":["Durham, Ryan","0000-0003-2739-8437
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"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1153"],"dc:subject":["NMDA Receptor","Glutamate Receptors","smFRET","FRET","Allostery","Single-Molecule Methods","Biochemistry","Medicine and Health Sciences"],"dc:title":["Agonist-Induced Conformational Changes In The Nmda Receptor"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:48:47Z"}