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	Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.
ジャーナル・号・ページ	Nature, Vol. 552, Issue 7685, Page 368-373, Year 2017
掲載日	2017年12月21日
著者	Haijuan Yang / Xiaolu Jiang / Buren Li / Hyo J Yang / Meredith Miller / Angela Yang / Ankita Dhar / Nikola P Pavletich /
PubMed 要旨	The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the ...The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.
リンク	Nature / PubMed:29236692 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	1.75 - 3.8 Å
構造データ	7086 6bcu EMDB-7086: active dimer PDB-6bcu: Cryo-EM structure of the activated RHEB-mTORC1 refined to 3.4 angstrom 手法: EM (単粒子) / 解像度: 3.8 Å 7087 6bcx EMDB-7087, PDB-6bcx: mTORC1 structure refined to 3.0 angstroms 手法: EM (単粒子) / 解像度: 3.23 Å PDB-5wbh: Structure of the FRB domain of mTOR bound to a substrate recruitment peptide of S6K1 手法: X-RAY DIFFRACTION / 解像度: 1.75 Å PDB-5wbi: Crystal structure of the Arabidopsis thaliana Raptor 手法: X-RAY DIFFRACTION / 解像度: 3.0 Å PDB-5wbj: Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human 4EBP1 手法: X-RAY DIFFRACTION / 解像度: 3.0 Å PDB-5wbk: Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human S6K1 手法: X-RAY DIFFRACTION / 解像度: 3.11 Å PDB-5wbl: Crystal structure of the Arabidopsis thaliana Raptor in complex with the TOS peptide of human PRAS40 手法: X-RAY DIFFRACTION / 解像度: 3.35 Å PDB-5wbu: Crystal structure of mTOR(deltaN)-mLST8-PRAS40(alpha-helix & beta-strand) complex 手法: X-RAY DIFFRACTION / 解像度: 3.42 Å PDB-5wby: Crystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complex 手法: X-RAY DIFFRACTION / 解像度: 3.1 Å
化合物	ChemComp-HOH: WATER ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, 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-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子YM
由来	homo sapiens (ヒト) arabidopsis thaliana (シロイヌナズナ)
キーワード	TRANSFERASE / PROTEIN BINDING / FRB / Raptor / TOS / complex / WD40 / PRAS40 / PRAS40 beta / PIKK