Movie
Controller
Structure viewers
About EMN Papers
+Search query
-Structure paper
| Title | Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes. |
|---|---|
| Journal, issue, pages | Nature, Vol. 556, Issue 7699, Page 64-69, Year 2018 |
| Publish date | Apr 5, 2018 |
 Authors | Kuang Shen / Rick K Huang / Edward J Brignole / Kendall J Condon / Max L Valenstein / Lynne Chantranupong / Aimaiti Bomaliyamu / Abigail Choe / Chuan Hong / Zhiheng Yu / David M Sabatini /  |
| PubMed Abstract | Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase- ...Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase. |
 External links | Nature / PubMed:29590090 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.0 - 4.4 Å |
| Structure data | |
| Chemicals |  ChemComp-GNP: |
| Source |
|
 Keywords | SIGNALING PROTEIN / mTORC1 amino-acid sensing lysosome growth control |
homo sapiens (human)
