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6WJ2

CryoEM structure of the SLC38A9-RagA-RagC-Ragulator complex in the pre-GAP state

Summary for 6WJ2
Entry DOI10.2210/pdb6wj2/pdb
Related6WJ3
EMDB information21686 21687
DescriptorRagulator complex protein LAMTOR1, 9-{5-O-[(S)-hydroxy{[(R)-hydroxy(thiophosphonooxy)phosphoryl]oxy}phosphoryl]-alpha-L-arabinofuranosyl}-3,9-dihydro-1H-purine-2,6-dione, MAGNESIUM ION, ... (11 entities in total)
Functional Keywordssmall gtpase, mtorc1 activation, amino acid signaling, lysosome, signaling protein
Biological sourceHomo sapiens (Human)
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Total number of polymer chains8
Total formula weight173278.65
Authors
Fromm, S.A.,Hurley, J.H. (deposition date: 2020-04-11, release date: 2020-09-02, Last modification date: 2024-03-06)
Primary citationFromm, S.A.,Lawrence, R.E.,Hurley, J.H.
Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9.
Nat.Struct.Mol.Biol., 27:1017-1023, 2020
Cited by
PubMed Abstract: The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin (FLCN) complex (LFC) consists of the inactive Rag dimer, the pentameric scaffold Ragulator, and the FLCN:FNIP2 (FLCN-interacting protein 2) GTPase activating protein (GAP) complex, and prevents Rag dimer activation during amino acid starvation. How the LFC is disassembled upon amino acid refeeding is an outstanding question. Here we show that the cytoplasmic tail of the human lysosomal solute carrier family 38 member 9 (SLC38A9) destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RagC. We present the cryo-EM structures of Rags in complex with their lysosomal anchor complex Ragulator and the cytoplasmic tail of SLC38A9 in the pre- and post-GTP hydrolysis state of RagC, which explain how SLC38A9 destabilizes the LFC and so promotes Rag dimer activation.
PubMed: 32868926
DOI: 10.1038/s41594-020-0490-9
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.2 Å)
Structure validation

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PDB entries from 2024-11-06

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