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
ISSN2041-1723
卷号8
发表状态已发表
DOI10.1038/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
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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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