+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-9648 | |||||||||
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タイトル | Cryo-EM structure of gamma secretase in complex with a Notch fragment | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 Defective LFNG causes SCDO3 / positive regulation of L-glutamate import across plasma membrane / Cajal-Retzius cell differentiation / 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 ...Defective LFNG causes SCDO3 / positive regulation of L-glutamate import across plasma membrane / Cajal-Retzius cell differentiation / 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 / amyloid precursor protein biosynthetic process / 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 / positive regulation of coagulation / protein catabolic process at postsynapse / negative regulation of core promoter binding / 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 / gamma-secretase complex / 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 / aspartic endopeptidase activity, intramembrane cleaving / regulation of epithelial cell proliferation involved in prostate gland development / short-term synaptic potentiation / auditory receptor cell fate commitment / positive regulation of aorta morphogenesis / 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 amyloid precursor protein biosynthetic process / positive regulation of smooth muscle cell differentiation / cellular response to tumor cell / positive regulation of apoptotic process involved in morphogenesis / choline transport / compartment pattern specification / Noncanonical activation of NOTCH3 / positive regulation of endopeptidase activity / vasculogenesis involved in coronary vascular morphogenesis / T-helper 17 type immune response / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / epithelial to mesenchymal transition involved in endocardial cushion formation / Notch receptor processing / regulation of extracellular matrix assembly / endocardial cell differentiation / cardiac ventricle morphogenesis / central nervous system myelination / sequestering of calcium ion / membrane protein intracellular domain proteolysis / mesenchymal cell development / synaptic vesicle targeting / cardiac left ventricle morphogenesis / epidermal cell fate specification / negative regulation of axonogenesis / negative regulation of collagen biosynthetic process / coronary vein morphogenesis / regulation of resting membrane potential / cardiac vascular smooth muscle cell development / negative regulation of myotube differentiation / somatic stem cell division / left/right axis specification / negative regulation of cell adhesion molecule production / negative regulation of cardiac muscle hypertrophy / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / T cell activation involved in immune response / positive regulation of endothelial cell differentiation / interleukin-17-mediated signaling pathway / apoptotic process involved in embryonic digit morphogenesis / endocardium development / skin morphogenesis / NOTCH4 Activation and Transmission of Signal to the Nucleus / positive regulation of cardiac epithelial to mesenchymal transition / cardiac epithelial to mesenchymal transition / Pre-NOTCH Processing in Golgi / growth factor receptor binding / neural retina development / regulation of synaptic vesicle cycle / dorsal/ventral neural tube patterning / cellular response to follicle-stimulating hormone stimulus / negative regulation of calcium ion-dependent exocytosis / cardiac muscle cell myoblast differentiation / pericardium morphogenesis / cardiac atrium morphogenesis / negative regulation of catalytic activity / L-glutamate import across plasma membrane 類似検索 - 分子機能 | |||||||||
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 | |||||||||
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 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_9648.map.gz | 117.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-9648-v30.xml emd-9648.xml | 18.8 KB 18.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_9648.png | 69.8 KB | ||
その他 | emd_9648_additional.map.gz | 111.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-9648 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9648 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_9648.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.091 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: #1
ファイル | emd_9648_additional.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : gamma-secretase
+超分子 #1: gamma-secretase
+分子 #1: Nicastrin
+分子 #2: Presenilin-1
+分子 #3: Gamma-secretase subunit APH-1A
+分子 #4: Gamma-secretase subunit PEN-2
+分子 #5: Notch1
+分子 #6: N-ACETYL-D-GLUCOSAMINE
+分子 #7: BETA-D-MANNOSE
+分子 #8: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #9: CHOLESTEROL
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 1.5625 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期 角度割当 | タイプ: PROJECTION MATCHING |
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最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 476853 |