dc.creator | Oldham, William Michael | |
dc.date.accessioned | 2020-08-22T00:27:05Z | |
dc.date.available | 2010-05-02 | |
dc.date.issued | 2008-05-02 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-04072008-141141 | |
dc.identifier.uri | http://hdl.handle.net/1803/12040 | |
dc.description.abstract | Heterotrimeric G proteins act as molecular switches in signaling pathways by coupling the activation of heptahelical receptors at the cell surface to intracellular responses. These receptors bind to and activate G proteins by catalyzing GTP for GDP exchange on the Gα subunit, leading to a structural change in Gα(GTP) and Gβγ subunits that allows the activation of a variety of downstream effector proteins. Despite its crucial role in a variety of signal transduction pathways, relatively little is known about the structure of the receptor-G protein complex and how this interaction leads to GDP release from Gα. Thus, the primary goal of this research has been to use the biophysical technique of site-directed spin-labeling to identify and characterize receptor-dependent conformational changes in Gα with electron paramagnetic resonance spectroscopy. With this approach, α5 helix of Gα has been shown to play a key role in coupling receptor-binding to GDP release. In addition, the structure and dynamics of several other important regions of this protein have been explored throughout the G protein activation pathway. These studies enhance the current understanding of G protein structure and function, which has been largely based on high resolution structural data from x-ray crystallography, by providing dynamic information about this protein in solution. This combination of structural approaches should continue to provide important insight into the biomechanics of G protein signaling and will hopefully serve as the starting point for more sophisticated models of the critically important receptor-G protein complex. | |
dc.format.mimetype | application/pdf | |
dc.subject | heterotrimer | |
dc.subject | GPCR | |
dc.subject | rhodopsin | |
dc.subject | transducin | |
dc.title | Mapping Conformational Changes Along the Activation Pathway of the Heterotrimeric G Protein α Subunit with Site-directed Spin-labeling | |
dc.type | dissertation | |
dc.contributor.committeeMember | Jeff Conn | |
dc.contributor.committeeMember | Hassane Mchaourab | |
dc.contributor.committeeMember | Heidi E. Hamm | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Pharmacology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2010-05-02 | |
local.embargo.lift | 2010-05-02 | |
dc.contributor.committeeChair | Vsevolod Gurevich | |