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DOI | 10.1038/s41467-019-11426-z |
Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2 | |
Karuppasamy, Manikandan1; Kusmider, Beata2; Oliveira, Taiana M.1; Gaubitz, Christl2; Prouteau, Manoel2; Loewith, Robbie2,3; Schaffitzel, Christiane1,4 | |
2019-08-08 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | France; Switzerland; England |
英文摘要 | The target of rapamycin (TOR) kinase assembles into two distinct multiprotein complexes, conserved across eukaryote evolution. In contrast to TOR complex 1 (TORC1), TORC2 kinase activity is not inhibited by the macrolide rapamycin. Here, we present the structure of Saccharomyces cerevisiae TORC2 determined by electron cryo-microscopy. TORC2 contains six subunits assembling into a 1.4 MDa rhombohedron. Tor2 and Lst8 form the common core of both TOR complexes. Avo3/Rictor is unique to TORC2, but interacts with the same HEAT repeats of Tor2 that are engaged by Kog1/Raptor in mammalian TORC1, explaining the mutual exclusivity of these two proteins. Density, which we conclude is Avo3, occludes the FKBP12-rapamycin-binding site of Tor2's FRB domain rendering TORC2 rapamycin insensitive and recessing the kinase active site. Although mobile, Avo1/hSin1 further restricts access to the active site as its conserved-region-in-the-middle (CRIM) domain is positioned along an edge of the TORC2 active-site-cleft, consistent with a role for CRIM in substrate recruitment. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000416229300015 |
WOS关键词 | MAMMALIAN PROTEIN ; BINDING PARTNER ; TOR ; MTOR ; RAPTOR ; GROWTH ; YEAST ; RESOLUTION ; PATHWAY ; PREDICTION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
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/204493 |
专题 | 资源环境科学 |
作者单位 | 1.European Mol Biol Lab, Grenoble Outstat, 71 Ave Martyrs, F-38042 Grenoble, France; 2.Univ Geneva, Inst Genet & Genom Geneva iGE3, Dept Mol Biol, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland; 3.Univ Geneva, Swiss Natl Ctr Competence Res NCCR Chem Biol, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland; 4.Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England |
推荐引用方式 GB/T 7714 | Karuppasamy, Manikandan,Kusmider, Beata,Oliveira, Taiana M.,et al. Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Karuppasamy, Manikandan.,Kusmider, Beata.,Oliveira, Taiana M..,Gaubitz, Christl.,Prouteau, Manoel.,...&Schaffitzel, Christiane.(2019).Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2.NATURE COMMUNICATIONS,8. |
MLA | Karuppasamy, Manikandan,et al."Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2".NATURE COMMUNICATIONS 8(2019). |
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