Structural basis for the assembly of the Ragulator-Rag GTPase complex

Ryo Yonehara, Shigeyuki Nada, Tomokazu Nakai, Masahiro Nakai, Ayaka Kitamura, Akira Ogawa, Hirokazu Nakatsumi, Keiichi Nakayama, Songling Li, Daron M. Standley, Eiki Yamashita, Atsushi Nakagawa, Masato Okada

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The mechanistic target of rapamycin complex 1 (mTORC1) plays a central role in regulating cell growth and metabolism by responding to cellular nutrient conditions. The activity of mTORC1 is controlled by Rag GTPases, which are anchored to lysosomes via Ragulator, a pentameric protein complex consisting of membrane-anchored p18/LAMTOR1 and two roadblock heterodimers. Here we report the crystal structure of Ragulator in complex with the roadblock domains of RagA-C, which helps to elucidate the molecular basis for the regulation of Rag GTPases. In the structure, p18 wraps around the three pairs of roadblock heterodimers to tandemly assemble them onto lysosomes. Cellular and in vitro analyses further demonstrate that p18 is required for Ragulator-Rag GTPase assembly and amino acid-dependent activation of mTORC1. These results establish p18 as a critical organizing scaffold for the Ragulator-Rag GTPase complex, which may provide a platform for nutrient sensing on lysosomes.

Original languageEnglish
Article number1625
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

lysosomes
GTP Phosphohydrolases
assembly
Lysosomes
nutrients
Nutrients
wrap
organizing
metabolism
Aminoacylation
Food
amino acids
Cell growth
platforms
Metabolism
Scaffolds
activation
membranes
proteins
acids

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Yonehara, R., Nada, S., Nakai, T., Nakai, M., Kitamura, A., Ogawa, A., ... Okada, M. (2017). Structural basis for the assembly of the Ragulator-Rag GTPase complex. Nature communications, 8(1), [1625]. https://doi.org/10.1038/s41467-017-01762-3

Structural basis for the assembly of the Ragulator-Rag GTPase complex. / Yonehara, Ryo; Nada, Shigeyuki; Nakai, Tomokazu; Nakai, Masahiro; Kitamura, Ayaka; Ogawa, Akira; Nakatsumi, Hirokazu; Nakayama, Keiichi; Li, Songling; Standley, Daron M.; Yamashita, Eiki; Nakagawa, Atsushi; Okada, Masato.

In: Nature communications, Vol. 8, No. 1, 1625, 01.12.2017.

Research output: Contribution to journalArticle

Yonehara, R, Nada, S, Nakai, T, Nakai, M, Kitamura, A, Ogawa, A, Nakatsumi, H, Nakayama, K, Li, S, Standley, DM, Yamashita, E, Nakagawa, A & Okada, M 2017, 'Structural basis for the assembly of the Ragulator-Rag GTPase complex', Nature communications, vol. 8, no. 1, 1625. https://doi.org/10.1038/s41467-017-01762-3
Yonehara R, Nada S, Nakai T, Nakai M, Kitamura A, Ogawa A et al. Structural basis for the assembly of the Ragulator-Rag GTPase complex. Nature communications. 2017 Dec 1;8(1). 1625. https://doi.org/10.1038/s41467-017-01762-3
Yonehara, Ryo ; Nada, Shigeyuki ; Nakai, Tomokazu ; Nakai, Masahiro ; Kitamura, Ayaka ; Ogawa, Akira ; Nakatsumi, Hirokazu ; Nakayama, Keiichi ; Li, Songling ; Standley, Daron M. ; Yamashita, Eiki ; Nakagawa, Atsushi ; Okada, Masato. / Structural basis for the assembly of the Ragulator-Rag GTPase complex. In: Nature communications. 2017 ; Vol. 8, No. 1.
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