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-Structure paper
タイトル | Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 11, Page 1017-1023, Year 2020 |
掲載日 | 2020年8月31日 |
著者 | Simon A Fromm / Rosalie E Lawrence / James H Hurley / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:32868926 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.9 Å |
構造データ | EMDB-21686, PDB-6wj2: EMDB-21687, PDB-6wj3: |
化合物 | ChemComp-GDP: ChemComp-L8S: ChemComp-MG: ChemComp-U3J: |
由来 |
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キーワード | SIGNALING PROTEIN / small GTPase / mTORC1 activation / amino acid signaling / lysosome |