title: Structural mechanism of G protein activation by G protein-coupled receptor.
abstract: G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate physiology and pathology of various organs. Consequently, about 40% of drugs in the market targets GPCRs. Heterotrimeric G proteins are composed of α, β, and γ subunits, and act as the key downstream signaling molecules of GPCRs. The structural mechanism of G protein activation by GPCRs has been of a great interest, and a number of biochemical and biophysical studies have been performed since the late 80's. These studies investigated the interface between GPCR and G proteins and the structural mechanism of GPCR-induced G protein activation. Recently, arrestins are also reported to be important molecular switches in GPCR-mediated signal transduction, and the physiological output of arrestin-mediated signal transduction is different from that of G protein-mediated signal transduction. Understanding the structural mechanism of the activation of G proteins and arrestins would provide fundamental information for the downstream signaling-selective GPCR-targeting drug development. This review will discuss the structural mechanism of GPCR-induced G protein activation by comparing previous biochemical and biophysical studies.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Duc
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Hee Ryung
authors.initials: HR
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 440-746, Republic of Korea. Electronic address: kychung2@skku.edu.
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Chung
mesh_terms: D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins
keywords: G protein; GPCR; Structure