• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Phase-plate cryo-EM structure of a class B GPCR-G-protein complex
【24h】

Phase-plate cryo-EM structure of a class B GPCR-G-protein complex

机译：B类GPCR-G蛋白复合物的相板冷冻EM结构

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric G alpha(s)beta gamma protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7. This conformation is accompanied by a 60 degrees kink in helix 6 and a large outward movement of the intracellular end of this helix, opening the bundle to accommodate interactions with the alpha 5-helix of G alpha(s). Also observed is an extended intracellular helix 8 that contributes to both receptor stability and functional G-protein coupling via an interaction with the G beta subunit. This structure provides a new framework for understanding G-protein-coupled receptor function.
机译：B类G蛋白偶联受体是治疗慢性疾病（如骨质疏松症，糖尿病和肥胖症）的主要靶标。在这里，我们报告的全长B类受体，降钙素受体的结构，与肽配体和由Volta相板单颗粒低温电子显微镜确定的异三聚体G alpha（s）βγ蛋白复合。肽激动剂通过结合跨膜螺旋6和7的胞外末端的大向外运动而促进的延伸疏水口袋的结合而与受体结合。该构象伴随着螺旋6的60度扭结和细胞内大的向外运动螺旋的末端，打开束以容纳与G alpha的alpha 5螺旋的相互作用。还观察到了延伸的细胞内螺旋8，其通过与Gβ亚基的相互作用而有助于受体稳定性和功能性G蛋白偶联。该结构为理解G蛋白偶联受体功能提供了新的框架。

著录项

  • 来源
    《Nature》 |2017年第7656期|118-123|共6页
  • 作者

    Liang Yi-Lynn; Khoshouei Maryam; Radjainia Mazdak; Zhang Yan; Glukhova Alisa; Tarrasch Jeffrey; Thal David M.; Furness Sebastian G. B.; Christopoulos George; Coudrat Thomas; Danev Radostin; Baumeister Wolfgang; Miller Laurence J.; Christopoulos Arthur; Kobilka Brian K.; Wootten Denise; Skiniotis Georgios; Sexton Patrick M.;

  • 作者单位

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany;

    Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia|FEI, NL-5651 GG Eindhoven, Netherlands;

    Univ Michigan, Inst Life Sci, Sch Med, Ann Arbor, MI 48109 USA|Univ Michigan, Dept Biol Chem, Sch Med, Ann Arbor, MI 48109 USA;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Univ Michigan, Inst Life Sci, Sch Med, Ann Arbor, MI 48109 USA|Univ Michigan, Dept Biol Chem, Sch Med, Ann Arbor, MI 48109 USA;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany;

    Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany;

    Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

    Univ Michigan, Inst Life Sci, Sch Med, Ann Arbor, MI 48109 USA|Univ Michigan, Dept Biol Chem, Sch Med, Ann Arbor, MI 48109 USA;

    Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia|Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号