Structural basis for the docking of mTORC1 on the lysosomal surface
What this study shows
3.2-angstrom cryo-EM structure of Raptor bound to Rag-Ragulator, showing how Raptor reads out the nutrient-dependent nucleotide state of the Rag GTPases: one part of Raptor senses RagA's nucleotide state, a separate 'claw' senses RagC's, and both have to be in the correct nutrient-signalling combination before Raptor is allowed to dock. Mutating the contact points blocks mTORC1 from reaching the lysosome and inhibits its signalling, which is the functional evidence behind the structural claim. Combined with a separate structure of mTORC1 bound to its activator Rheb, the paper builds a model of the complete, active mTORC1 sitting on the lysosome. Boundary: cryo-EM of a complex reconstituted from purified human proteins, not a live-cell measurement.
At a glance
| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Cryo-EM structure (human proteins, cell-free reconstitution) + cell-based mutagenesis) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Cryo-EM structure (human proteins, cell-free reconstitution) + cell-based mutagenesis |
| Journal | Science |
| Year | 2019 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1126/science.aay0166 · PMID 31601708 · Free full text (PMC7176403) |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Structural (cryo-EM, reconstituted complex) + mutagenesis |
| Target | mTORC1 / Raptor / Rag-Ragulator |
| Model | Human proteins, cell-free reconstitution |
| Effect | 3.2 A structure showing how Raptor reads the nucleotide state of RagA and RagC to dock mTORC1 on the lysosome; docking-disrupting mutations block mTORC1 lysosomal localization and signalling |
In the Atlas
Related topics
More studies on this topic
- Structural basis for mTORC1 activation on the lysosomal membrane (2025)
- Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids (2010)
- Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex (2023)
- A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids (2022)
Learn the biology
Want to understand the biology behind this study? → The Lysosome as a Signalling Platform
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