Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/s41586-020-1954-0 |
Structure of the M2 muscarinic receptor-beta-arrestin complex in a lipid nanodisc | |
Gate, David1,2; Saligrama, Naresha3; Leventhal, Olivia1; Yang, Andrew C.4,5; Unger, Michael S.6,7; Middeldorp, Jinte1,2,8; Chen, Kelly1; Lehallier, Benoit1,2; Channappa, Divya1; De Los Santos, Mark B.1; McBride, Alisha1,2; Pluvinage, John1,9,10; Elahi, Fanny11; Tam, Grace Kyin-Ye1,12; Kim, Yongha1,12; Greicius, Michael1,12; Wagner, Anthony D.13,14; Aigner, Ludwig6,7; Galasko, Douglas R.15; Davis, Mark M.3,16,17; Wyss-Coray, Tony1,2,5,14,18 | |
2020-01-16 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2020 |
卷号 | 579期号:7798页码:297-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文关键词 | After activation by an agonist, G-protein-coupled receptors (GPCRs) recruit beta-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis(1). Additionally, beta-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins(2). In contrast to G proteins, for which there are many high-resolution structures in complex with GPCRs, the molecular mechanisms underlying the interaction of beta-arrestin with GPCRs are much less understood. Here we present a cryo-electron microscopy structure of beta-arrestin 1 (beta arr1) in complex with M2 muscarinic receptor (M2R) reconstituted in lipid nanodiscs. The M2R-beta arr1 complex displays a multimodal network of flexible interactions, including binding of the N domain of beta arr1 to phosphorylated receptor residues and insertion of the finger loop of beta arr1 into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric G(o) protein complex(3). Moreover, the cryo-electron microscopy map reveals that the C-edge of beta arr1 engages the lipid bilayer. Through atomistic simulations and biophysical, biochemical and cellular assays, we show that the C-edge is critical for stable complex formation, beta arr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest that the cooperative interactions of beta-arrestin with both the receptor and the phospholipid bilayer contribute to its functional versatility. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000519378900035 |
WOS关键词 | CRYSTAL-STRUCTURE ; WEB SERVER ; BETA-ARRESTIN-1 ; IDENTIFICATION ; RECRUITMENT ; MECHANISM ; SOFTWARE ; PROTEINS ; ROLES ; MODEL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281169 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA; 2.Vet Adm Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA; 3.Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA; 4.Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA; 5.Stanford Univ, Chem Engn & Med Human Hlth, Stanford, CA 94305 USA; 6.Paracelsus Med Univ, Inst Mol Regenerat Med, Salzburg, Austria; 7.Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Salzburg, Austria; 8.Univ Utrecht, Univ Med Ctr Utrecht, Dept Translat Neurosci, Brain Ctr, Utrecht, Netherlands; 9.Stanford Univ, Sch Med, Med Scientist Training Program, Stanford, CA 94305 USA; 10.Stanford Univ, Sch Med, Stem Cell Biol & Regenerat Med Grad Program, Stanford, CA 94305 USA; 11.Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA; 12.Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Funct Imaging Neuropsychiat Disorders Lab, Stanford, CA 94305 USA; 13.Stanford Univ, Dept Psychol, Stanford, CA USA; 14.Stanford Univ, Wu Tsai Neurosci Inst, Stanford, CA 94305 USA; 15.Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA; 16.Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA; 17.Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA; 18.Stanford Univ, Sch Med, Paul F Glenn Ctr Biol Aging, Stanford, CA 94305 USA |
推荐引用方式 GB/T 7714 | Gate, David,Saligrama, Naresha,Leventhal, Olivia,et al. Structure of the M2 muscarinic receptor-beta-arrestin complex in a lipid nanodisc[J]. NATURE,2020,579(7798):297-+. |
APA | Gate, David.,Saligrama, Naresha.,Leventhal, Olivia.,Yang, Andrew C..,Unger, Michael S..,...&Wyss-Coray, Tony.(2020).Structure of the M2 muscarinic receptor-beta-arrestin complex in a lipid nanodisc.NATURE,579(7798),297-+. |
MLA | Gate, David,et al."Structure of the M2 muscarinic receptor-beta-arrestin complex in a lipid nanodisc".NATURE 579.7798(2020):297-+. |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论