[논문]Structural Aspects of GPCR-G Protein Coupling

Chung, Ka Young

doi:10.5487/tr.2013.29.3.149

Structural Aspects of GPCR-G Protein Coupling 원문보기

Toxicological research, v.29 no.3, 2013년, pp.149 - 155

Chung, Ka Young (School of Pharmacy, Sungkyunkwan University)

Abstract ▼ AI-Helper

G protein-coupled receptors (GPCRs) are membrane receptors; approximately 40% of drugs on the market target GPCRs. A precise understanding of the activation mechanism of GPCRs would facilitate the development of more effective and less toxic drugs. Heterotrimeric G proteins are important molecular switches in GPCR-mediated signal transduction. An agonist-activated receptor interacts with specific sites on G proteins and promotes the release of GDP from the $G{\alpha}$ subunit. Because of the important biological role of the GPCR-G protein coupling, conformational changes in the G protein upon receptor coupling have been of great interest. One of the most important questions was the interface between the GPCR and G proteins and the structural mechanism of GPCR-induced G protein activation. A number of biochemical and biophysical studies have been performed since the late 80s to address these questions; there was a significant breakthrough in 2011 when the crystal structure of a GPCR-G protein complex was solved. This review discusses the structural aspects of GPCR-G protein coupling by comparing the results of previous biochemical and biophysical studies to the GPCR-G protein crystal structure.

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문제 정의

Due to the technical difficulties of obtaining crystals of membrane proteins, however, afewmammalian GPCR structures have been obtained mostly during past 6 years (17), and there is only one crystal structure of the receptor-G protein complex (18). This review will summarize the recent advance in the understanding of the structural aspect of G protein activation by GPCRs.

가설 설정

Second, GPCRs do not only act as a monomer but also as oligomers (56-58). What would be the coupling mode between G proteins and oligomerized GPCRs? Would GPCR oligomerization affect the G protein selectivity? Third, recent studies suggested that G proteins can interact with inactive GPCRs as a pre-assembled complex (27,59-62). The preassembly of GPCR-G protein can speed-up the signal transduction and provide G protein selectivity of GPCRs (63).

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