登録情報 データベース : EMDB / ID : EMD-9648 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of gamma secretase in complex with a Notch fragment マップデータ 詳細 試料複合体 : gamma-secretaseタンパク質・ペプチド : Nicastrinタンパク質・ペプチド : Presenilin-1タンパク質・ペプチド : Gamma-secretase subunit APH-1Aタンパク質・ペプチド : Gamma-secretase subunit PEN-2タンパク質・ペプチド : Notch1リガンド : N-ACETYL-D-GLUCOSAMINEリガンド : BETA-D-MANNOSEリガンド : 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINEリガンド : CHOLESTEROL 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / cardiac right ventricle formation / growth involved in heart morphogenesis / Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation / cell differentiation in spinal cord / retinal cone cell differentiation / venous endothelial cell differentiation / arterial endothelial cell differentiation ... Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / cardiac right ventricle formation / growth involved in heart morphogenesis / Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation / cell differentiation in spinal cord / retinal cone cell differentiation / venous endothelial cell differentiation / arterial endothelial cell differentiation / cardiac chamber formation / epithelial cell fate commitment / negative regulation of pro-B cell differentiation / Pre-NOTCH Processing in the Endoplasmic Reticulum / negative regulation of inner ear auditory receptor cell differentiation / mitral valve formation / cell migration involved in endocardial cushion formation / glomerular mesangial cell development / negative regulation of photoreceptor cell differentiation / negative regulation of cell proliferation involved in heart valve morphogenesis / regulation of somitogenesis / inhibition of neuroepithelial cell differentiation / endocardium morphogenesis / atrioventricular node development / foregut morphogenesis / regulation of cell adhesion involved in heart morphogenesis / distal tubule development / MAML1-RBP-Jkappa- ICN1 complex / Cajal-Retzius cell differentiation / regulation of epithelial cell proliferation involved in prostate gland development / positive regulation of L-glutamate import across plasma membrane / auditory receptor cell fate commitment / protein catabolic process at postsynapse / positive regulation of aorta morphogenesis / amyloid precursor protein biosynthetic process / negative regulation of endothelial cell chemotaxis / neuroendocrine cell differentiation / collecting duct development / negative regulation of extracellular matrix constituent secretion / positive regulation of transcription of Notch receptor target / positive regulation of coagulation / negative regulation of core promoter binding / gamma-secretase complex / cellular response to tumor cell / positive regulation of apoptotic process involved in morphogenesis / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / compartment pattern specification / vasculogenesis involved in coronary vascular morphogenesis / T-helper 17 type immune response / positive regulation of amyloid precursor protein biosynthetic process / regulation of extracellular matrix assembly / positive regulation of endopeptidase activity / endocardial cell differentiation / Noncanonical activation of NOTCH3 / epithelial to mesenchymal transition involved in endocardial cushion formation / cardiac ventricle morphogenesis / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / positive regulation of smooth muscle cell differentiation / cardiac left ventricle morphogenesis / mesenchymal cell development / sequestering of calcium ion / Notch receptor processing / epidermal cell fate specification / choline transport / coronary vein morphogenesis / central nervous system myelination / negative regulation of collagen biosynthetic process / synaptic vesicle targeting / cardiac vascular smooth muscle cell development / negative regulation of myotube differentiation / somatic stem cell division / left/right axis specification / membrane protein intracellular domain proteolysis / negative regulation of axonogenesis / regulation of resting membrane potential / negative regulation of cardiac muscle hypertrophy / negative regulation of cell adhesion molecule production / interleukin-17-mediated signaling pathway / positive regulation of endothelial cell differentiation / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / apoptotic process involved in embryonic digit morphogenesis / endocardium development / T cell activation involved in immune response / positive regulation of cardiac epithelial to mesenchymal transition / Pre-NOTCH Processing in Golgi / cardiac epithelial to mesenchymal transition / NOTCH4 Activation and Transmission of Signal to the Nucleus / skin morphogenesis / cellular response to follicle-stimulating hormone stimulus / negative regulation of calcium ion-dependent exocytosis / pericardium morphogenesis / cardiac atrium morphogenesis / growth factor receptor binding / cardiac muscle cell myoblast differentiation / neural retina development / negative regulation of catalytic activity / dorsal/ventral neural tube patterning / regulation of synaptic vesicle cycle / neuronal stem cell population maintenance 類似検索 - 分子機能 Neurogenic locus notch homolog protein 1 / Peptidase A22A, presenilin 1 / Gamma-secretase subunit Aph-1 / Gamma-secretase aspartyl protease complex, presenilin enhancer-2 subunit / Aph-1 protein / Presenilin enhancer-2 subunit of gamma secretase / Peptidase A22A, presenilin / Notch, C-terminal / Presenilin, C-terminal / Presenilin ... Neurogenic locus notch homolog protein 1 / Peptidase A22A, presenilin 1 / Gamma-secretase subunit Aph-1 / Gamma-secretase aspartyl protease complex, presenilin enhancer-2 subunit / Aph-1 protein / Presenilin enhancer-2 subunit of gamma secretase / Peptidase A22A, presenilin / Notch, C-terminal / Presenilin, C-terminal / Presenilin / Domain of unknown function / Nicastrin / Nicastrin, small lobe / Nicastrin / Nicastrin small lobe / Notch / Presenilin/signal peptide peptidase / Notch, NOD domain / Notch, NODP domain / NOTCH protein / NOTCH protein / Presenilin, signal peptide peptidase, family / NOD / NODP / Notch-like domain superfamily / LNR (Lin-12/Notch) repeat profile. / LNR domain / Notch domain / Domain found in Notch and Lin-12 / EGF-like, conserved site / Human growth factor-like EGF / : / Calcium-binding EGF domain / Ankyrin repeats (many copies) / EGF-like domain / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / Ankyrin repeat / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 2. / EGF-like domain signature 1. / EGF-like domain / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily 類似検索 - ドメイン・相同性 Neurogenic locus notch homolog protein 1 / Presenilin-1 / Nicastrin / Gamma-secretase subunit APH-1A / Gamma-secretase subunit PEN-2 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.7 Å 詳細 データ登録者Yang G / Zhou R / Zhou Q / Guo X / Yan C / Ke M / Lei J / Shi Y 引用ジャーナル : Nature / 年 : 2019タイトル : Structural basis of Notch recognition by human γ-secretase.著者 : Guanghui Yang / Rui Zhou / Qiang Zhou / Xuefei Guo / Chuangye Yan / Meng Ke / Jianlin Lei / Yigong Shi / 要旨 : Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of ... Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase. 履歴 登録 2018年9月9日 - ヘッダ(付随情報) 公開 2018年12月26日 - マップ公開 2018年12月26日 - 更新 2019年1月23日 - 現状 2019年1月23日 処理サイト : PDBj / 状態 : 公開
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