NMR spectroscopy for structural and dynamic studies of the beta2-adrenergic receptor
Abstract/Contents
- Abstract
- G protein coupled receptors (GPCRs) are seven transmembrane proteins that are expressed in all eukaryotic cells and tissues. These receptors play key roles in human physiology and disease. The goal of my work is to understand the molecular detail of ligand recognition by GPCRs, and how this process leads to conformational changes that manifest as cellular signaling. Meeting this goal will advance our knowledge of membrane protein biology. It will also reveal structural targets and physicochemical logic to aid pharmaceutical design. The age of GPCR structural biology recently arrived with the first x-ray structures of rhodopsin and the beta2 adrenergic receptor (beta2AR). However, membrane proteins are constantly fluctuating entities. Dynamic behavior is intrinsic to their function. As such, static x-ray structures alone are inadequate. Herein, I develop biophysical techniques to study these dynamic receptors. Using NMR spectroscopy, I characterize conformational changes in the extracellular region of the beta2AR, a surface rich with potential for drug design. I also explore the signaling properties of monomeric GPCRs and conformational changes of other macromolecules using single-molecule fluorescence. While many questions about GPCRs remain, I hope this work is a small step towards understanding these important, fascinating, and beautiful molecules.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Bokoch, Michael Paul |
|---|---|
| Associated with | Stanford University, Department of Biophysics. |
| Primary advisor | Kobilka, Brian K |
| Thesis advisor | Kobilka, Brian K |
| Thesis advisor | Maduke, Merritt C, 1966- |
| Thesis advisor | Puglisi, Joseph D |
| Thesis advisor | Weis, William I |
| Advisor | Maduke, Merritt C, 1966- |
| Advisor | Puglisi, Joseph D |
| Advisor | Weis, William I |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Michael Paul Bokoch. |
|---|---|
| Note | Submitted to the Department of Biophysics. |
| Thesis | Ph. D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Michael Paul Bokoch
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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