Protein-Protein Interactions in Live Cells: Reinventing the Wheel

Son Ç. D.

6th International Drug Design Congress, İstanbul, Turkey, 13 - 15 December 2018

  • Publication Type: Conference Paper / Full Text
  • City: İstanbul
  • Country: Turkey
  • Middle East Technical University Affiliated: Yes


G protein-coupled receptors (GPCRs) are membrane proteins that mediate physiological

response to a diverse array of stimuli. In humans, they mediate the action of hundreds of

peptide hormones, sensory stimuli, odorants, neurotransmitters, and chemokines. GPCRs also

are targets for ~40% of all currently marketed pharmaceuticals. These receptors traditionally

been thought to act as monomeric units. However, recent evidence suggests that GPCRs may

form dimers as part of their normal trafficking and function. While the formation of GPCR

dimers/oligomers have been reported to play important roles in regulating receptor

expression, ligand binding, and second messenger activation, less is known about how GPCR

dimers interact with other proteins such as G-proteins and Arrestin.

We are interested in studiying the interactions between GPCRs and effect of this dimerization

on G-protein dimerization. Our group also focus on the mechanisms of receptor-arrestin

binding in live cells using Föster resonance energy transfer (FRET) and bimolecular

fluorescence complementation (BiFC) assays. We designed and developed tagged receptors,

G-proteins and Arrestin proteins using Green florescent protein variants that can be used in

imaging studies. These constructs are suitable for testing drug candidates and/or analyze

protein-protein interfaces for GPCRs or G-protein dimers.