GPCRs are seven-transmembrane proteins that mediate the functions of a large number of extracellular stimuli (light, hormones, neurotransmitters, etc.). The human genome contains about 800 distinct GPCR genes, and about 40 percent of drugs on the market target specific GPCRs. Despite significant progress made in recent decades in understanding the structure and function of GPCRs, some major questions remain unanswered. I apply site-directed mutagenesis and biochemical cross-linking approaches to address the following major questions:
- How do GPCRs interact with G proteins and arrestins?
- What is the structural basis and functional relevance of GPCR dimerization?