登録情報 データベース : EMDB / ID : EMD-28580 ダウンロードとリンクタイトル Structure of human ADAM10-Tspan15 complex bound to 11G2 vFab マップデータMap post-processed with DeepEMhancer using the high resolution model 詳細 試料複合体 : ADAM10-Tspan15-11G2 Fab complex複合体 : Disintegrin and metalloproteinase domain-containing protein 10 (E.C.3.4.24.81), Tetraspanin-15タンパク質・ペプチド : Disintegrin and metalloproteinase domain-containing protein 10タンパク質・ペプチド : Tetraspanin-15複合体 : 11G2 Fab Heavy Chain, 11G2 Fab Light Chainタンパク質・ペプチド : 11G2 Fab Heavy Chainタンパク質・ペプチド : 11G2 Fab Light Chainリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : CALCIUM IONリガンド : ZINC IONリガンド : 4-(N-HYDROXYAMINO)-2R-ISOBUTYL-2S-(2-THIENYLTHIOMETHYL)SUCCINYL-L-PHENYLALANINE-N-METHYLAMIDEリガンド : CHOLESTEROL HEMISUCCINATE 残り2件を表示 表示を減らす 詳細 キーワード Protease / Metalloprotease / Tetraspanin / Sheddase / Adhesion / MEMBRANE PROTEIN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
regulation of membrane protein ectodomain proteolysis / ADAM10 endopeptidase / constitutive protein ectodomain proteolysis / regulation of vasculature development / epidermal growth factor receptor ligand maturation / monocyte activation / metalloendopeptidase activity involved in amyloid precursor protein catabolic process / postsynapse organization / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / protein catabolic process at postsynapse ... regulation of membrane protein ectodomain proteolysis / ADAM10 endopeptidase / constitutive protein ectodomain proteolysis / regulation of vasculature development / epidermal growth factor receptor ligand maturation / monocyte activation / metalloendopeptidase activity involved in amyloid precursor protein catabolic process / postsynapse organization / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / protein catabolic process at postsynapse / pore complex assembly / perinuclear endoplasmic reticulum / positive regulation of T cell chemotaxis / tetraspanin-enriched microdomain / regulation of Notch signaling pathway / NOTCH4 Activation and Transmission of Signal to the Nucleus / metallodipeptidase activity / adherens junction organization / negative regulation of cell adhesion / regulation of postsynapse organization / clathrin-coated vesicle / Golgi-associated vesicle / Signaling by EGFR / pore complex / amyloid precursor protein catabolic process / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / response to tumor necrosis factor / Collagen degradation / tertiary granule membrane / membrane protein ectodomain proteolysis / cochlea development / EPH-ephrin mediated repulsion of cells / extracellular matrix disassembly / negative regulation of Notch signaling pathway / specific granule membrane / Notch signaling pathway / Degradation of the extracellular matrix / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / protein maturation / integrin-mediated signaling pathway / protein localization to plasma membrane / adherens junction / NOTCH3 Activation and Transmission of Signal to the Nucleus / Post-translational protein phosphorylation / synaptic membrane / metalloendopeptidase activity / protein processing / SH3 domain binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / metallopeptidase activity / late endosome membrane / integrin binding / cell junction / cell-cell signaling / positive regulation of cell growth / endopeptidase activity / in utero embryonic development / postsynaptic density / nuclear body / protein phosphorylation / positive regulation of cell migration / Amyloid fiber formation / endoplasmic reticulum lumen / Golgi membrane / axon / signaling receptor binding / negative regulation of gene expression / focal adhesion / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / dendrite / Neutrophil degranulation / protein kinase binding / glutamatergic synapse / enzyme binding / cell surface / Golgi apparatus / protein homodimerization activity / extracellular exosome / metal ion binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 : / Metallo-peptidase family M12B Reprolysin-like / ADAM10, cysteine-rich domain / Tetraspanin, animals / Tetraspanin, EC2 domain superfamily / Tetraspanin/Peripherin / Tetraspanin family / ADAM10/ADAM17 catalytic domain / : / Disintegrin ... : / Metallo-peptidase family M12B Reprolysin-like / ADAM10, cysteine-rich domain / Tetraspanin, animals / Tetraspanin, EC2 domain superfamily / Tetraspanin/Peripherin / Tetraspanin family / ADAM10/ADAM17 catalytic domain / : / Disintegrin / Disintegrin domain profile. / Homologues of snake disintegrins / Disintegrin domain / Disintegrin domain superfamily / Peptidase M12B, ADAM/reprolysin / ADAM type metalloprotease domain profile. / Metallopeptidase, catalytic domain superfamily / Neutral zinc metallopeptidases, zinc-binding region signature. 類似検索 - ドメイン・相同性 Disintegrin and metalloproteinase domain-containing protein 10 / Tetraspanin-15 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.3 Å 詳細 データ登録者Lipper CH / Blacklow SC 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Cancer Institute (NIH/NCI) R35 CA220340 米国 Other private Gift from Edward B. Goodnow
引用ジャーナル : Cell / 年 : 2023タイトル : Structural basis for membrane-proximal proteolysis of substrates by ADAM10.著者 : Colin H Lipper / Emily D Egan / Khal-Hentz Gabriel / Stephen C Blacklow / 要旨 : The endopeptidase ADAM10 is a critical catalyst for the regulated proteolysis of key drivers of mammalian development, physiology, and non-amyloidogenic cleavage of APP as the primary α-secretase. ... The endopeptidase ADAM10 is a critical catalyst for the regulated proteolysis of key drivers of mammalian development, physiology, and non-amyloidogenic cleavage of APP as the primary α-secretase. ADAM10 function requires the formation of a complex with a C8-tetraspanin protein, but how tetraspanin binding enables positioning of the enzyme active site for membrane-proximal cleavage remains unknown. We present here a cryo-EM structure of a vFab-ADAM10-Tspan15 complex, which shows that Tspan15 binding relieves ADAM10 autoinhibition and acts as a molecular measuring stick to position the enzyme active site about 20 Å from the plasma membrane for membrane-proximal substrate cleavage. Cell-based assays of N-cadherin shedding establish that the positioning of the active site by the interface between the ADAM10 catalytic domain and the bound tetraspanin influences selection of the preferred cleavage site. Together, these studies reveal the molecular mechanism underlying ADAM10 proteolysis at membrane-proximal sites and offer a roadmap for its modulation in disease. 履歴 登録 2022年10月14日 - ヘッダ(付随情報) 公開 2023年6月14日 - マップ公開 2023年6月14日 - 更新 2024年11月13日 - 現状 2024年11月13日 処理サイト : RCSB / 状態 : 公開
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