Please wait a minute...
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (1): 39-43    DOI: 10.3785/j.issn.1008-9292.2019.02.07
Single-particle cryo-electron microscopy opens new avenues in structural biology of G protein-coupled receptor
LI Chuntao1(),ZHANG Huibing1,ZHANG Yan1,2()
1.Department of Biophysics, Zhejiang University School of Medicine, Hangzhou 310058, China;
2.Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Download: HTML( 22 )   PDF(1360KB)
Export: BibTeX | EndNote (RIS)      


G protein-coupled receptors (GPCRs) represent the largest class of cell surface receptors, mediating wide range of cellular and physiological processes through their transducers, G proteins and the-arrestins participate in almost all pathological processes. Recent technological advances are revolutionizing the utility of cryo-electron microscopy (cryo-EM), leading to a tremendous progress in the structural studies of biological macromolecules and cryo-EM has played a leading role in the structural biology of GPCR signaling complex. New discoveries of high-resolution three-dimensional structures of GPCR signaling complexes based on cryo-EM have emerged vigorously, which depict the common structural characteristics of intermolecular interaction between GPCR and G protein complex-the conformational changes of the transmembrane helix 6 of receptors, and also demonstrate the structural basis of G protein subtype selectivity. Single-particle cryo-EM becomes an efficient tool for identifying the molecular mechanism of receptor-ligand interaction, providing important information for understanding GPCR signaling and the structure-based drug design.

Key wordsReceptors, G-protein-coupled      Freezing      Microscopy, electron      GTP-binding proteins     
Received: 30 September 2018      Published: 10 May 2019
CLC:  Q71  
Corresponding Authors: ZHANG Yan     E-mail:;
Cite this article:

LI Chuntao,ZHANG Huibing,ZHANG Yan. Single-particle cryo-electron microscopy opens new avenues in structural biology of G protein-coupled receptor. J Zhejiang Univ (Med Sci), 2019, 48(1): 39-43.

URL:     OR



关键词: 受体,G-蛋白偶联,  冷冻,  显微镜检查,电子,  GTP结合蛋白质类 
Figure 1 Density maps of G protein-coupled receptors complexes revealed by cryo-electron microscopy
[1]   HAUSER A S , CHAVALI S , MASUHO I , et al . Pharmacogenomics of GPCR drug targets[J]. Cell,2018,172(1-2):41-54.e19.
[2]   DEISENHOFER J , EPP O, MIKI K , et al . X-ray structure analysis of a membrane protein complex. Electron density map at 3 ? resolution and a model of the chromophores of the photosynthetic reaction center from Rhodopseudomonas viridis [J]. J Mol Biol,1984,180(2):385-398.
[3]   OKADA T , LE T I , FOX B A, et al . X-ray diffraction analysis of three-dimensional crystals of bovine rhodopsin obtained from mixed micelles[J]. J Struct Biol,2000,130(1):73-80.
[4]   GHOSH E , KUMARI P , JAIMAN D , et al . Methodological advances: the unsung heroes of the GPCR structural revolution[J]. Nat Rev Mol Cell Biol,2015,16(2):69-81.
[5]   RASMUSSEN S G , DEVREE B T , ZOU Y , et al . Crystal structure of the β2 adrenergic receptor-Gs protein complex[J]. Nature,2011,477(7366),549-555.
[6]   CARPENTER B , NEHMé R , WARNE T , et al . Structure of the adenosine A(2A) receptor bound to an engineered G protein[J]. Nature,2016,536(7614):104-107.
[7]   LIANG Y L , KHOSHOUEI M , RADJAINIA M , et al . Phase-plate cryo-EM structure of a class B GPCR-G-protein complex[J]. Nature,2017,546(7656):118-123.
[8]   ZHANG Y , SUN B , FENG D , et al . Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein[J]. Nature,2017,546(7657):248-253.
[9]   LIANG Y L , KHOSHOUEI M , GLUKHOVA A , et al . Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex[J]. Nature,2018,555(7694):121-125.
[10]   GARCíA-NAFRíA J , LEE Y, BAI X , et al . Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein[J/OL]. Elife,2018,7:e35946.
[11]   SAFDARI H A , PANDEY S , SHUKLA A K , et al . Illuminating GPCR Signaling by cryo-EM[J]. Trends Cell Biol,2018,28(8):591-594.
[12]   KANG Y , KUYBEDA O , WAAL P W DE , et al . Publisher correction: cryo-EM structure of human rhodopsin bound to an inhibitory G protein[J/OL]. Nature,2018,561(7724):E44.
[13]   KOEHL A , HU H , MAEDA S , et al . Structure of the μ-opioid receptor-Gi protein complex[J]. Nature,2018,558(7711):547-552.
[14]   DRAPER-JOYCE C J , KHOSHOUEI M , THAL D M , et al . Structure of the adenosine-bound human adenosine A1 receptor-Gi complex[J]. Nature,2018,558(7711):559-563.
[15]   GARCíA-NAFRíA J , NEHMé R , EDWARDS P C , et al . Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go [J]. Nature,2018,558(7711):620-623.
[16]   KUMARI P , SRIVASTAVA A , BANERJEE R , et al . Functional competence of a partially engaged GPCR-beta-arrestin complex[J]. Nat Commun,2016,7:13416.
[17]   THOMSEN A R B , PLOUFFE B , CAHILL T J 3RD, et al . GPCR-G protein-β-arrestin super-complex mediates sustained G protein signaling[J]. Cell, 2016,166(4):907-919.
[18]   CAHILL T J 3RD, THOMSEN A R , TARRASCH J T , et al . Distinct conformations of GPCR-beta-arrestin complexes mediate desensitization, signaling, and endocytosis[J]. Proc Natl Acad Sci U S A, 2017,114(10):2562-2567.
[1] SHI Jing,FENG Jue. New inhibitors targeting bacterial RNA polymerase[J]. J Zhejiang Univ (Med Sci), 2019, 48(1): 44-49.
[2] Lu Xinfa, Hu Zhongrong, Wang Kening, et al. FREEZING-THAWING METHOD FOR SPLITTING OF EPIDEMIC HEMORRHAGIC FEVER VIRUS AND ITS MECHANISM[J]. J Zhejiang Univ (Med Sci), 1990, 19(2): 49-52.