6WJ3

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

6WJ3 の概要

• エントリーDOI: 10.2210/pdb6wj3/pdb
• 関連するPDBエントリー: 6WJ2
• EMDBエントリー: 21686 21687
• 分子名称: Ragulator complex protein LAMTOR1, xanthosine diphosphate, Ragulator complex protein LAMTOR2, ... (10 entities in total)
• 機能のキーワード: small gtpase, mtorc1 activation, amino acid signaling, 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: 173158.30

構造登録者

Fromm, S.A.,Hurley, J.H. (登録日: 2020-04-11, 公開日: 2020-09-02, 最終更新日: 2024-03-06)

主引用文献

Fromm, 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

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

実験手法

ELECTRON MICROSCOPY (3.9 Å)