6U62

Raptor-Rag-Ragulator complex

Summary for 6U62

• Entry DOI: 10.2210/pdb6u62/pdb
• EMDB information: 20660 20661
• Descriptor: Regulatory-associated protein of mTOR, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (11 entities in total)
• Functional Keywords: signaling complex, gtpase, lysosome, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 305712.06

Authors

Rogala, K.B.,Sabatini, D.M. (deposition date: 2019-08-29, release date: 2019-10-30, Last modification date: 2024-03-20)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.18 Å)