Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand
文献类型：期刊论文
| 作者 | Zhang, Xianjun1,2,11,12; Zhao, Fei11; Wu, Yiran11; Tan, Wenfu11; Tao, Houchao11; Xu, Fei11,12; Zhao, Suwen12; Ye, Lintao12; Lin, Xi1,2,12; Ding, Kang12 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:-页码:15383 |
| 关键词 | Genome-wide association study Dense 3D facial image Ancestry-divergent phenotypes Face prediction Forensic scenario |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/ncomms15383 |
| 文献子类 | Article |
| 英文摘要 | The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 angstrom. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | SERIAL FEMTOSECOND CRYSTALLOGRAPHY ; BASAL-CELL CARCINOMA ; LIPIDIC CUBIC PHASE ; MEMBRANE-PROTEINS ; FORCE-FIELD ; HEDGEHOG ; MODULATION ; MESOPHASES ; SOFTWARE ; AMBER |
| 语种 | 英语 |
| WOS记录号 | WOS:000401512300001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/937]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China; 4.Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90089 USA; 5.Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90089 USA; 6.Chinese Acad Sci, Shanghai Inst Mat Medica, Univ Chinese Acad Sci, 555 Zuchongzhi Lu, Bldg 3,Room 426, Shanghai 201203, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Biol Sci, Univ Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China; 8.Scripps Res Inst, Dept Mol Therapeut, 130 Scripps Way, Jupiter, FL 33458 USA; 9.MRC, Mol Biol Lab, Biomedical Campus,Francis Crick Ave, Cambridge 33458, England; 10.MRC, Mol Biol Lab, Biomedical Campus,Francis Crick Ave, Cambridge, England; |
| 推荐引用方式 GB/T 7714 | Zhang, Xianjun,Zhao, Fei,Wu, Yiran,et al. Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand[J]. NATURE COMMUNICATIONS,2017,8(-):15383. |
| APA | Zhang, Xianjun.,Zhao, Fei.,Wu, Yiran.,Tan, Wenfu.,Tao, Houchao.,...&,.(2017).Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand.NATURE COMMUNICATIONS,8(-),15383. |
| MLA | Zhang, Xianjun,et al."Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand".NATURE COMMUNICATIONS 8.-(2017):15383. |
入库方式： OAI收割
来源：上海营养与健康研究所
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