EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex.
ジャーナル・号・ページ	Nature, Vol. 614, Issue 7948, Page 572-579, Year 2023
掲載日	2023年1月25日
著者	Zhicheng Cui / Gennaro Napolitano / Mariana E G de Araujo / Alessandra Esposito / Jlenia Monfregola / Lukas A Huber / Andrea Ballabio / James H Hurley /
PubMed 要旨	The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1) is unique in its ...The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1) is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the 'megacomplex'. Two full Rag-Ragulator complexes present each molecule of TFEB to the mTOR active site. One Rag-Ragulator complex is bound to Raptor in the canonical mode seen previously in the absence of TFEB. A second Rag-Ragulator complex (non-canonical) docks onto the first through a RagC GDP-dependent contact with the second Ragulator complex. The non-canonical Rag dimer binds the first helix of TFEB with a RagC-dependent aspartate clamp in the cleft between the Rag G domains. In cellulo mutation of the clamp drives TFEB constitutively into the nucleus while having no effect on mTORC1 localization. The remainder of the 108-amino acid TFEB docking domain winds around Raptor and then back to RagA. The double use of RagC GDP contacts in both Rag dimers explains the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state.
リンク	Nature / PubMed:36697823 / PubMed Central
手法	EM (単粒子)
解像度	2.8 - 3.7 Å
構造データ	EMDB-26840: Focused refinement of the Raptor-TFEB-Rag-Ragulator complex with Raptor mask 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-26842: Focused refinement of the Raptor-TFEB-Rag-Ragulator complex with c-Rag-Ragulator mask 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-26843: Focused refinement of the Raptor-TFEB-Rag-Ragulator complex with TFEB-nc-Rag-Ragulator mask 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-26844: Homogeneous refinement of the Raptor-TFEB-Rag-Ragulator complex 手法: EM (単粒子) / 解像度: 3.1 Å 26846 7ux2 EMDB-26846: Composite cryo-EM map of the Raptor-TFEB-Rag-Ragulator complex PDB-7ux2: cryo-EM structure of the Raptor-TFEB-Rag-Ragulator complex 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-26852: Cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex with C2 symmetry 手法: EM (単粒子) / 解像度: 3.7 Å 26857 7uxc EMDB-26857, PDB-7uxc: cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex with symmetry expansion 手法: EM (単粒子) / 解像度: 3.2 Å 26861 7uxh EMDB-26861: A composite cryo-EM map of the mTORC1-TFEB-Rag-Ragulator complex PDB-7uxh: cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex 手法: EM (単粒子) / 解像度: 3.2 Å
化合物	ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP / GDP, エネルギー貯蔵分子YM ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE / フィチン酸
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / mTORC1 / TFEB / Lysosome biogenesis / Autophagy