Conformational Dynamics of the Glutamate Receptors via single Molecule Förster Resonance Energy Transfer
Landes, Christy F
Doctor of Philosophy
Glutamate receptors perform a critical role in the nervous system, mediating synaptic transmission through cellular membranes. These proteins have developed a quick response to agonist presence and, when activated, undergo a conformational shift that allows calcium ion transport across the membrane. In a number of neurological diseases, genetic variants can cause mutations that disrupt the balance between fast binding response and desensitization resulting in over- or under- signaling in affected cells. Herein it describes the use of single molecule Förster resonance energy transfer to observe the bound form of the glutamate receptors and subsequent dynamics. For a complete understanding of the dynamics involved in the conformational landscape, the response of the receptor to a variety of known full and partial agonists is tested. Additionally multiple receptor types are investigated to determine if the conformational pathway is conserved between the different types of glutamate receptors. The results from this project allows for a more complete understanding of the relationship between conformation and functionality of glutamate receptors.
glutamate receptors; single molecule; FRET;