Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia.
Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Research Center Jülich, 52425 Jülich, Germany; JuStruct: Jülich Center for Structural Biology, Research Center Jülich, 52425 Jülich, Germany.
Curr Opin Struct Biol. 2020 Aug;63:18-25. doi: 10.1016/j.sbi.2020.03.004. Epub 2020 Apr 16.
G protein-coupled receptors (GPCRs) constitute the largest superfamily of membrane proteins that are involved in regulation of sensory and physiological processes and implicated in many diseases. The last decade revolutionized the GPCR field by unraveling multiple high-resolution structures of many different receptors in complexes with various ligands and signaling partners. A complete understanding of the complex nature of GPCR function is, however, impossible to attain without combining static structural snapshots with information about GPCR dynamics obtained by complementary spectroscopic techniques. As illustrated in this review, structure and dynamics studies are now paving the way for understanding important questions of GPCR biology such as partial and biased agonism, allostery, oligomerization, and other fundamental aspects of GPCR signaling.
G 蛋白偶联受体(GPCRs)是最大的膜蛋白超家族,参与调节感觉和生理过程,并与许多疾病有关。过去十年,通过解析多种不同受体与各种配体和信号伙伴复合物的多个高分辨率结构,彻底改变了 GPCR 领域。然而,如果不将静态结构快照与通过互补光谱技术获得的关于 GPCR 动力学的信息结合起来,就不可能完全理解 GPCR 功能的复杂性质。正如本综述所说明的,结构和动力学研究现在为理解 GPCR 生物学的重要问题铺平了道路,如部分和偏向激动剂、变构、寡聚化和 GPCR 信号的其他基本方面。