7T3C

GATOR1-RAG-RAGULATOR - Dual Complex

Summary for 7T3C

• Entry DOI: 10.2210/pdb7t3c/pdb
• EMDB information: 25654
• Descriptor: GATOR complex protein NPRL2, Ras-related GTP-binding protein C, GUANOSINE-5'-DIPHOSPHATE, ... (13 entities in total)
• Functional Keywords: complex, gtpase activating protein, nutrient sensing, metabolism, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 17
• Total formula weight: 582764.76

Authors

Egri, S.B.,Shen, K. (deposition date: 2021-12-07, release date: 2022-04-06, Last modification date: 2025-05-28)

Primary citation

Egri, S.B.,Ouch, C.,Chou, H.T.,Yu, Z.,Song, K.,Xu, C.,Shen, K.
Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a spatial-constraint regulated GAP mechanism.
Mol.Cell, 82:1836-, 2022

PubMed Abstract: mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface by the Ragulator complex. The Rag GTPases receive amino acid signals from multiple upstream regulators. One negative regulator, GATOR1, is a GTPase activating protein (GAP) for RagA. GATOR1 binds to the Rag GTPases via two modes: an inhibitory mode and a GAP mode. How these two binding interactions coordinate to process amino acid signals is unknown. Here, we resolved three cryo-EM structural models of the GATOR1-Rag-Ragulator complex, with the Rag-Ragulator subcomplex occupying the inhibitory site, the GAP site, and both binding sites simultaneously. When the Rag GTPases bind to GATOR1 at the GAP site, both Rag subunits contact GATOR1 to coordinate their nucleotide loading states. These results reveal a potential GAP mechanism of GATOR1 during the mTORC1 inactivation process.

PubMed: 35338845
DOI: 10.1016/j.molcel.2022.03.002

Experimental method

ELECTRON MICROSCOPY (4 Å)