Item Details

abstract

G protein coupled receptors (GPCRs) are a superfamily of transmembrane proteins responsible for transducing extracellular stimuli into intracellular responses. GPCRs are indispensable to a vast variety of distinct physiologies and behaviors and represent approximately 50% of all human drug targets. However, considerable debate exists as to the structural basis for GPCR activation, with a classical monomeric (two state model) conflicting with a growing number of reports indicating that these receptors form higher order functional oligomers. These receptor-receptor interactions can impact receptor trafficking, ligand sensitivity, desensitization, and strength of effector response. As such, an understanding of GPCR oligomerization is indispensable to our overall understanding of receptor dynamics. Additionally, the specific molecular events underlying receptor activation and signaling remain incompletely understood. Since the initial discovery of the GPCR receptor family, a number of conserved amino acid motifs have been identified that have been shown to play specific and critical roles in GPCR activation, intracellular G-protein coupling, and receptor desensitization. Still, many of these motifs remain incompletely described, with some motifs having only been evaluated in a small subset of receptors, and experimental evidence suggests that in some cases, these conserved motifs may have divergent roles in specific receptor subfamilies. As such, the conservation of these motifs throughout GPCR evolution represents and interesting and unresolved aspect of GPCR function.

subject

contributor

Rizzo, Michael Joseph (author)

Johnson, Erik C (committee chair)

Muday, Gloria K (committee member)

Lord, Pat C (committee member)

Zhang, Ke (committee member)

date

2020-01-08T09:35:27Z (accessioned)

2020-01-08T09:35:27Z (available)

2019 (issued)

degree

Biology (discipline)

identifier

http://hdl.handle.net/10339/95959 (uri)

language

en (iso)

publisher

Wake Forest University

title

MOLECULAR DISSECTION OF G-PROTEIN COUPLED RECEPTOR SIGNALING AND OLIGOMERIZATION

type

Dissertation