Understanding the activation-deactivation mechanism of glutamate receptor proteins at the single molecule level

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dc.contributor.advisorLandes, Christy F.en_US
dc.creatorChatterjee, Sudeshnaen_US
dc.date.accessioned2019-05-17T19:05:07Zen_US
dc.date.available2020-05-01T05:01:09Zen_US
dc.date.created2019-05en_US
dc.date.issued2019-04-15en_US
dc.date.submittedMay 2019en_US
dc.date.updated2019-05-17T19:05:08Zen_US
dc.description.abstractIonotropic glutamate receptor proteins form ion channels at the neuronal membrane and mediate excitatory synaptic neurotransmission in the mammalian central nervous system. These receptor proteins, such as NMDA and AMPA receptors, are structurally diverse and house multiple extracellular and intracellular binding sites, which can modulate activated (open) or deactivated (closed) states of the ion channel. The gating action (activation and deactivation) of the ion channels are controlled by a number of molecules (ligands) interacting with specific binding sites. Hence, these binding sites can serve as potential drug targets for controlling the aberrant activation of the ion channel that leads to a number of neurological disorders. In this research, we have utilized single molecule Förster Resonance Energy Transfer (smFRET) spectroscopy to provide a mechanistic understanding of the activation processes that the receptors undergo. We have probed, at a single molecule level, the structural changes explored by the NMDA receptor proteins, upon binding with several ligands that induce different modes of activation and have provided a comprehensive mechanism for their gating action. Furthermore, we have reported the conformational behavior induced by phosphorylation, at the structurally unresolved C-terminal domain of the AMPA receptors. We have demonstrated the capability of single molecule spectroscopy for studying such complex protein structures and deciphering mechanisms that would otherwise remain unresolved by ensemble measurements. The results from this study are expected to contribute to the ever-expanding research of targeted neuro-therapy.en_US
dc.embargo.terms2020-05-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationChatterjee, Sudeshna. "Understanding the activation-deactivation mechanism of glutamate receptor proteins at the single molecule level." (2019) Diss., Rice University. <a href="https://hdl.handle.net/1911/105998">https://hdl.handle.net/1911/105998</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/105998en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectGlutamate receptorsen_US
dc.subjectNMDAen_US
dc.subjectAMPAen_US
dc.subjectsmFRETen_US
dc.titleUnderstanding the activation-deactivation mechanism of glutamate receptor proteins at the single molecule levelen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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