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Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1

Author

Listed:
  • Tianlong Zhang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Rong Wang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Zhijing Wang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences
    School of Life Science and Technology, ShanghaiTech University)

  • Xiangxiang Wang

    (School of Life Sciences, Shanghai University)

  • Fang Wang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Jianping Ding

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences
    School of Life Science and Technology, ShanghaiTech University)

Abstract

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 α1 of p18 and the two helices side of MP1-p14. The interaction of Ragulator with Rag GTPases is required for their cellular co-localization 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.

Suggested Citation

  • Tianlong Zhang & Rong Wang & Zhijing Wang & Xiangxiang Wang & Fang Wang & Jianping Ding, 2017. "Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01567-4
    DOI: 10.1038/s41467-017-01567-4
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    Cited by:

    1. Jasjot Singh & Hadeer Elhabashy & Pathma Muthukottiappan & Markus Stepath & Martin Eisenacher & Oliver Kohlbacher & Volkmar Gieselmann & Dominic Winter, 2022. "Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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