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基本情報
登録情報 | データベース: PDB / ID: 6idf | |||||||||
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タイトル | Cryo-EM structure of gamma secretase in complex with a Notch fragment | |||||||||
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![]() | MEMBRANE PROTEIN / complex | |||||||||
機能・相同性 | ![]() 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 | |||||||||
生物種 | ![]() | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.7 Å | |||||||||
![]() | Yang, G. / Zhou, R. / Zhou, Q. / Guo, X. / Yan, C. / Ke, M. / Lei, J. / Shi, Y. | |||||||||
資金援助 | ![]()
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![]() | ![]() 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. | |||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 259.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 209.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.5 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.5 MB | 表示 | |
XML形式データ | ![]() | 45.8 KB | 表示 | |
CIF形式データ | ![]() | 66.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 3種, 3分子 ABE
#1: タンパク質 | 分子量: 78483.570 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#2: タンパク質 | 分子量: 52644.543 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: P49768, 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; アスパラギン酸プロテアーゼ |
#5: タンパク質 | 分子量: 14758.500 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-Gamma-secretase subunit ... , 2種, 2分子 CD
#3: タンパク質 | 分子量: 29017.943 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#4: タンパク質 | 分子量: 12038.029 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-糖 , 3種, 12分子 ![](data/chem/img/NAG.gif)
#6: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #7: 多糖 | beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #8: 糖 | ChemComp-NAG / |
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-非ポリマー , 2種, 7分子 ![](data/chem/img/PC1.gif)
![](data/chem/img/CLR.gif)
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#9: 化合物 | ChemComp-PC1 / #10: 化合物 | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: gamma-secretase / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 1.5625 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 476853 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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