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	Regulation of human mTOR complexes by DEPTOR.
ジャーナル・号・ページ	Elife, Vol. 10, Year 2021
掲載日	2021年9月14日
著者	Matthias Wälchli / Karolin Berneiser / Francesca Mangia / Stefan Imseng / Louise-Marie Craigie / Edward Stuttfeld / Michael N Hall / Timm Maier /
PubMed 要旨	The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein ...The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein that binds and regulates both complexes of mammalian target of rapamycin (mTOR), a central regulator of cell growth. Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. The PDZ domain binds tightly with mildly activating effect, but then acts as an anchor for DEPt association that allosterically suppresses mTOR activation. The binding interfaces of the PDZ domain and DEPt also support further regulation by other signaling pathways. A separate, substrate-like mode of interaction for DEPTOR phosphorylation by mTOR complexes rationalizes inhibition of non-stimulated mTOR activity at higher DEPTOR concentrations. The multifaceted interplay between DEPTOR and mTOR provides a basis for understanding the divergent roles of DEPTOR in physiology and opens new routes for targeting the mTOR-DEPTOR interaction in disease.
リンク	Elife / PubMed:34519268 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	1.93 - 4.24 Å
構造データ	13347 7pe7 EMDB-13347, PDB-7pe7: cryo-EM structure of DEPTOR bound to human mTOR complex 2, overall refinement 手法: EM (単粒子) / 解像度: 3.41 Å 13348 7pe8 EMDB-13348, PDB-7pe8: cryo-EM structure of DEPTOR bound to human mTOR complex 2, focussed on one protomer 手法: EM (単粒子) / 解像度: 3.2 Å 13349 7pe9 EMDB-13349, PDB-7pe9: cryo-EM structure of DEPTOR bound to human mTOR complex 2, DEPt-bound subset local refinement 手法: EM (単粒子) / 解像度: 3.7 Å 13350 7pea EMDB-13350, PDB-7pea: cryo-EM structure of DEPTOR bound to human mTOR complex 1, overall refinement 手法: EM (単粒子) / 解像度: 4.07 Å 13351 7peb EMDB-13351, PDB-7peb: cryo-EM structure of DEPTOR bound to human mTOR complex 1, focussed on one protomer 手法: EM (単粒子) / 解像度: 3.67 Å 13352 7pec EMDB-13352, PDB-7pec: cryo-EM structure of DEPTOR bound to human mTOR complex 1, DEPt-bound subset local refinement 手法: EM (単粒子) / 解像度: 4.24 Å PDB-7ped: DEPTOR DEP domain tandem (DEPt) 手法: X-RAY DIFFRACTION / 解像度: 1.93 Å
化合物	ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE / フィチン酸 / フィチン酸 ChemComp-ZN: Unknown entry ChemComp-ACE: ACETYL GROUP / アセトアルデヒド / アセチル基 ChemComp-HOH: WATER / 水
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / DEPTOR / mTOR (MTOR) / regulator / inhibitor (酵素阻害剤) / mTORC2 / DEP-domain / PDZ-domain / mTORC1 (MTORC1) / mTOR-binding