6U62

Raptor-Rag-Ragulator complex

6U62 の概要

• エントリーDOI: 10.2210/pdb6u62/pdb
• EMDBエントリー: 20660 20661
• 分子名称: Regulatory-associated protein of mTOR, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (11 entities in total)
• 機能のキーワード: signaling complex, gtpase, lysosome, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 305712.06

構造登録者

Rogala, K.B.,Sabatini, D.M. (登録日: 2019-08-29, 公開日: 2019-10-30, 最終更新日: 2024-03-20)

主引用文献

Rogala, K.B.,Gu, X.,Kedir, J.F.,Abu-Remaileh, M.,Bianchi, L.F.,Bottino, A.M.S.,Dueholm, R.,Niehaus, A.,Overwijn, D.,Fils, A.P.,Zhou, S.X.,Leary, D.,Laqtom, N.N.,Brignole, E.J.,Sabatini, D.M.
Structural basis for the docking of mTORC1 on the lysosomal surface.
Science, 366:468-475, 2019

PubMed Abstract: The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where its Raptor subunit interacts with the Rag guanosine triphosphatase (GTPase)-Ragulator complex. Nutrients switch the heterodimeric Rag GTPases among four different nucleotide-binding states, only one of which (RagA/B•GTP-RagC/D•GDP) permits mTORC1 association. We used cryo-electron microscopy to determine the structure of the supercomplex of Raptor with Rag-Ragulator at a resolution of 3.2 angstroms. Our findings indicate that the Raptor α-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling. By comparison with a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on the lysosome.

PubMed: 31601708
DOI: 10.1126/science.aay0166

実験手法

ELECTRON MICROSCOPY (3.18 Å)