Cited by 134PI3K/AKT/mTOR signaling in cancerAutophagy in Disease and TherapyProtein Kinase Regulation and GTPase Signaling

Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling

de Araujo, Mariana E. G., Naschberger, Andreas, Fürnrohr, Barbara G., Stasyk, Taras, Dunzendorfer-Matt, Theresia, Lechner, Stefan, Welti, Stefan, Kremser, Leopold +5 more·2017·Science

Abstract

Structure of human mTORC1 components: The mTORC1 (mechanistic target of rapamycin complex 1) complex garners much attention as a signaling hub that coordinates input from growth-factor receptors and nutrient availability with metabolism and cell growth and proliferation. de Araujo et al. report the crystal structure of the LAMTOR (or “Ragulator”) complex that helps assemble mTORC1 at the lysosomal membrane for activation. The structure and functional studies reveal how LAMTOR1 wraps around the other subunits to hold them in place and interacts with the Rag guanosine triphosphatases in the complex. Science , this issue p. 377

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Crossref · 10.1126/science.aao1583

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  • The heptameric Ragulator-Rag complex structure showed Rag C-terminal roadblock domains binding to the LAMTOR2-LAMTOR3 heterodimer, building a tower of three roadblock domain-mediated heterodimers tied together by the extended LAMTOR1 subunit, and presenting the GTPase domains for interaction with RAPTOR.

    “The heptameric Ragulator-Rag complex structure showed Rag C-terminal roadblock domains binding to the LAMTOR2-LAMTOR3 heterodimer (de Araujo et al., 2017; Su et al., 2017; Yonehara et al., 2017) (Fig. 4B), thus building a tower of three roadblock domain-mediated heterodimers tied together by the extended LAMTOR1 subunit, and presenting the GTPase domains for interaction with RAPTOR.”

    From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as de Araujo et al., 2017

  • When the Rag heterodimer binds Ragulator, the N-terminal portion of LAMTOR1 encompassing residues 47-64 is resolved, forming an α-helix which packs against the RagC roadblock domain, whereas in the Ragulator complex alone this region of LAMTOR1 was disordered.

    “It is important to note that when the Rag heterodimer binds Ragulator, the N-terminal portion of LAMTOR1 encompassing residues 47-64 is resolved, forming an α-helix which packs against the RagC roadblock domain, whereas in the Ragulator complex alone this region of LAMTOR1 was disordered (de Araujo et al., 2017; Yonehara et al., 2017).”

    From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as de Araujo et al., 2017

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Authors
de Araujo, M. E. G., Naschberger, A., Fürnrohr, B. G., Stasyk, T., Dunzendorfer-Matt, T., Lechner, S., Welti, S., Kremser, L., Shivalingaiah, G., Offterdinger, M., Lindner, H. H., Huber, L. A., & Scheffzek, K.
Affiliations
  • Division of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Innsbruck Medical University (AT)
Corresponding author
  • Naschberger, Andreas
  • Fürnrohr, Barbara G.
  • Huber, Lukas A.
  • Scheffzek, Klaus
Venue
Science
Published
2017-10-20
Volume
358
Issue
6361
Pages
377-381
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2757150230
Cited by
134
References
61
Citations by year
2026: 13 · 2025: 11 · 2024: 13 · 2023: 11 · 2022: 20 · 2021: 14 · 2020: 15 · 2019: 19 · 2018: 9 · 2017: 9
FWCI
5.81
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
Austrian Science Fund (award337283, P26682, award337284, P28975)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
Ragulator complex, mTORC1, LAMTOR1, Rag GTPases, lysosomes, heterodimer assembly, mTOR signaling, crystal structure, protein complex formation
MeSH terms
Protein Domains, Mechanistic Target of Rapamycin Complex 1, Carrier Proteins, Humans, Lysosomes, Signal Transduction, Crystallography, X-Ray, GTP Phosphohydrolases, Intracellular Signaling Peptides and Proteins

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