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Structure of the human glucagon class B G-protein-coupled receptor
文献类型：期刊论文
| 作者 | Siu, Fai Yiu6; He, Min1,2; de Graaf, Chris3; Han, Gye Won6; Yang, Dehua1,2 ; Zhang, Zhiyun1,2; Zhou, Caihong1,2; Xu, Qingping4; Wacker, Daniel6; Joseph, Jeremiah S.6
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| 刊名 | NATURE
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| 出版日期 | 2013-07-25 |
| 卷号 | 499期号:7459页码:444-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature12393 |
| 文献子类 | Article |
| 英文摘要 | Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting; thus GCGR plays an important role in glucose homeostasis. Here we report the crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 angstrom resolution, complemented by extensive site-specific mutagenesis, and a hybrid model of glucagon bound to GCGR to understand the molecular recognition of the receptor for its native ligand. Beyond the shared seven transmembrane fold, the GCGR transmembrane domain deviates from class A G-protein-coupled receptors witha large ligand-binding pocket and the first transmembrane helix having a 'stalk' region that extends three alpha-helical turns above the plane of the membrane. The stalk positions the extracellular domain (similar to 12 kilodaltons) relative to the membrane to form the glucagon-binding site that captures the peptide and facilitates the insertion of glucagon's amino terminus into the seven transmembrane domain. |
| WOS关键词 | 2ND TRANSMEMBRANE HELIX ; LIGAND-BINDING ; PEPTIDE-1 RECEPTOR ; SECRETIN RECEPTOR ; AMINO-TERMINUS ; CRYSTALLIZING MEMBRANE ; EXTRACELLULAR LOOP ; PHOTOLABILE PROBES ; LIPIDIC MESOPHASES ; OPIOID RECEPTOR |
| 资助项目 | NIH Road map[P50GM073197] ; NIH Road map[U54 GM094618] ; NIH Road map[U54 GM094586] ; Ministry of Health[2012ZX09304-011] ; Ministry of Health[2013ZX09507002] ; Shanghai Science and Technology Development Fund[11DZ2292200] ; Novo Nordisk-Chinese Academy of Sciences Research Fund[NNCAS-2011-7] ; Thousand Talents Program in China[00000000] ; NIH[F32 DK088392] ; Netherlands Organization for Scientific Research (NWO) through a VENI[700.59.408] ; COST Action[CM1207] ; National Cancer Institute[Y1-CO-1020] ; National Institute of General Medical Sciences[Y1-GM-1104] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000322157900033 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277533]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Wang, Ming-Wei |
| 作者单位 | 1.Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.Vrije Univ Amsterdam, Amsterdam Inst Mol Med & Syst AIMMS, Fac Sci, Div Med Chem, NL-1081 HV Amsterdam, Netherlands; 4.SLAC Natl Accelerator Lab, Joint Ctr Struct Genom, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA; 5.Novo Nordisk, Prot & Peptide Chem, DK-2760 Malov, Denmark 6.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA; |
| 推荐引用方式 GB/T 7714 | Siu, Fai Yiu,He, Min,de Graaf, Chris,et al. Structure of the human glucagon class B G-protein-coupled receptor[J]. NATURE,2013,499(7459):444-+. |
| APA | Siu, Fai Yiu.,He, Min.,de Graaf, Chris.,Han, Gye Won.,Yang, Dehua.,...&Stevens, Raymond C..(2013).Structure of the human glucagon class B G-protein-coupled receptor.NATURE,499(7459),444-+. |
| MLA | Siu, Fai Yiu,et al."Structure of the human glucagon class B G-protein-coupled receptor".NATURE 499.7459(2013):444-+. |
入库方式： OAI收割
来源：上海药物研究所
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