7T3A

GATOR1-RAG-RAGULATOR - Inhibitory Complex

7T3A の概要

• エントリーDOI: 10.2210/pdb7t3a/pdb
• EMDBエントリー: 25652
• 分子名称: GATOR complex protein DEPDC5, Ragulator complex protein LAMTOR5, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (11 entities in total)
• 機能のキーワード: complex, gtpase activating protein, nutrient sensing, metabolism, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 435600.48

構造登録者

Egri, S.B.,Shen, K. (登録日: 2021-12-07, 公開日: 2022-04-06, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4 Å)