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Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1 | |
Zhang, Tianlong1; Wang, Rong1; Wang, Zhijing1,2; Wang, Xiangxiang3; Wang, Fang1; Ding, Jianping1,2 | |
2017-11-09 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
卷号 | 8 |
发表状态 | 已发表 |
DOI | 10.1038/s41467-017-01567-4 |
摘要 | Amino acid-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) is mediated by Rag GTPases, which are recruited to the lysosome by the Ragulator complex consisting of p18, MP1, p14, HBXIP and C7orf59; however, the molecular mechanism is elusive. Here, we report the crystal structure of Ragulator, in which p18 wraps around the MP1-p14 and C7orf59-HBXIP heterodimers and the interactions of p18 with MP1, C7orf59, and HBXIP are essential for the assembly of Ragulator. There are two binding sites for the Roadblock domains of Rag GTPases: helix alpha 1 of p18 and the two helices side of MP1-p14. The interaction of Ragulator with Rag GTPases is required for their cellular colocalization and can be competitively inhibited by C17orf59. Collectively, our data indicate that Ragulator functions as a scaffold to recruit Rag GTPases to lysosomal membrane in mTORC1 signaling. |
收录类别 | SCI |
语种 | 英语 |
资助项目 | Chinese Academy of Sciences[XDB08010302] |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000414807300012 |
出版者 | NATURE PUBLISHING GROUP |
WOS关键词 | CRYSTAL-STRUCTURE ; LYSOSOMAL SURFACE ; LATE ENDOSOMES ; AMINO-ACIDS ; COMPLEX ; ACTIVATION ; PROTEIN ; TORC1 ; AMPK ; METABOLISM |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10031 |
专题 | 生命科学与技术学院 生命科学与技术学院_特聘教授组_丁建平组 生命科学与技术学院_硕士生 |
通讯作者 | Ding, Jianping |
作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci,S, Natl Ctr Prot Sci Shanghai,Shanghai Sci Res Ctr,C, 320 Yue Yang Rd, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Hua Xia Zhong Rd, Shanghai 201210, Peoples R China 3.Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China |
通讯作者单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Zhang, Tianlong,Wang, Rong,Wang, Zhijing,et al. Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Zhang, Tianlong,Wang, Rong,Wang, Zhijing,Wang, Xiangxiang,Wang, Fang,&Ding, Jianping.(2017).Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1.NATURE COMMUNICATIONS,8. |
MLA | Zhang, Tianlong,et al."Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1".NATURE COMMUNICATIONS 8(2017). |
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