9OTI
GATOR2 complex bound to arginine sensor CASTOR1
Summary for 9OTI
| Entry DOI | 10.2210/pdb9oti/pdb |
| EMDB information | 70833 |
| Descriptor | GATOR2 complex protein MIOS, GATOR complex protein WDR24, GATOR complex protein WDR59, ... (7 entities in total) |
| Functional Keywords | complex, mtorc1, signaling, nutrients, amino acid sensing, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 18 |
| Total formula weight | 1175087.86 |
| Authors | Jansen, R.M.,Hurley, J.H. (deposition date: 2025-05-27, release date: 2025-10-01, Last modification date: 2025-10-29) |
| Primary citation | Jansen, R.M.,Maghe, C.,Tapia, K.,Wu, S.,Yang, S.,Ren, X.,Zoncu, R.,Hurley, J.H. Structural basis for mTORC1 regulation by the CASTOR1-GATOR2 complex. Nat.Struct.Mol.Biol., 32:1980-1988, 2025 Cited by PubMed Abstract: Mechanistic target of rapamycin complex 1 (mTORC1) is a nutrient-responsive master regulator of metabolism. Amino acids control the recruitment and activation of mTORC1 at the lysosome through the nucleotide loading state of the heterodimeric Rag GTPases. Under low nutrients, including arginine, the GTPase-activating protein complex GATOR1 promotes GTP hydrolysis on RagA/B, inactivating mTORC1. GATOR1 is regulated by the cage-like GATOR2 complex and cytosolic amino acid sensors. To understand how the arginine sensor CASTOR1 binds to GATOR2 to disinhibit GATOR1 under low cytosolic arginine, we determined the cryo-electron microscopy structure of human GATOR2 bound to CASTOR1 in the absence of arginine. Two MIOS WD40 domain β-propellers of the GATOR2 cage engage with both subunits of a single CASTOR1 homodimer. Each propeller binds to a negatively charged MIOS-binding interface on CASTOR1 that is distal to the arginine pocket. The structure shows how arginine-triggered loop ordering in CASTOR1 blocks the MIOS-binding interface, switches off its binding to GATOR2 and, thus, communicates to downstream mTORC1 activation. PubMed: 40715445DOI: 10.1038/s41594-025-01635-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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