Structure of the full-length glucagon class B G-protein-coupled receptor

doi:10.1038/nature22363

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	Structure of the full-length glucagon class B G-protein-coupled receptor
	Zhang, HN; Qiao, AN; Yang, DH; Yang, LL; Dai, AT; De Graaf, C; Reedtz-Runge, S; Dharmarajan, V; Zhang, H; Han, GW; Grant, TD; Sierra, RG; Weierstall, U; Nelson, G; Liu, W; Wu, YH; Ma, LM; Cai, XQ; Lin, GY; Wu, XA; Geng, Z; Dong, YH; Song, GJ; Griffin, PR; Lau, J; Chrezov, V; Yang, HY; Hanson, MA; Stevens, RC; Zhao, Q; Jiang, HL; Wang, MW; Wu, BL; Geng Z(耿直); Dong YH(董宇辉)
	2017
Source Publication	NATURE
ISSN	0028-0836
EISSN	1476-4687
Volume	546 Issue:7657 Pages:259-+
Subtype	Article
Abstract	The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 angstrom crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a beta-strand conformation, instead of forming an alpha-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a beta-hairpin conformation and interacts with the stalk to form a compact beta-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors.
DOI	10.1038/nature22363
WOS Keyword	SERIAL FEMTOSECOND CRYSTALLOGRAPHY ; CORTICOTROPIN-RELEASING-FACTOR ; LIPIDIC CUBIC PHASE ; EXTRACELLULAR DOMAINS ; DRUG DISCOVERY ; BINDING-SITE ; LIGAND ; REFINEMENT ; VALIDATION ; SOFTWARE
Indexed By	SCI ; PUBMED ; MEDLINE ; SCOPUS ; ADS
Language	英语
WOS Research Area	Science & Technology - Other Topics
WOS Subject	Multidisciplinary Sciences
WOS ID	WOS:000402823400031
ADS Bibcode	2017Natur.546..259Z
ADS URL	https://ui.adsabs.harvard.edu/abs/2017Natur.546..259Z
ADS CITATIONS	https://ui.adsabs.harvard.edu/abs/2017Natur.546..259Z/citations
MedlineID	MEDLINE:28514451
Citation statistics	Cited Times:20 [ADS]
Document Type	期刊论文
Identifier	http://ir.ihep.ac.cn/handle/311005/284872
Collection	多学科研究中心
Affiliation	中国科学院高能物理研究所
First Author Affilication	Institute of High Energy
Recommended Citation GB/T 7714	Zhang, HN,Qiao, AN,Yang, DH,et al. Structure of the full-length glucagon class B G-protein-coupled receptor[J]. NATURE,2017,546(7657):259-+.
APA	Zhang, HN.,Qiao, AN.,Yang, DH.,Yang, LL.,Dai, AT.,...&董宇辉.(2017).Structure of the full-length glucagon class B G-protein-coupled receptor.NATURE,546(7657),259-+.
MLA	Zhang, HN,et al."Structure of the full-length glucagon class B G-protein-coupled receptor".NATURE 546.7657(2017):259-+.

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