登録情報 データベース : EMDB / ID : EMD-37477 ダウンロードとリンクタイトル Structure of human phagocyte NADPH oxidase in the activated state マップデータcomposite map after focused refinement 詳細 試料複合体 : activated NOX2-p22 complexリガンド : x 7種 詳細 キーワード NOX2 / p22 / CYBA / CYBB / TP1170 / NOX / p67 / Rac / p47 / OXIDOREDUCTASE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
smooth muscle hypertrophy / reactive oxygen species biosynthetic process / cellular response to L-glutamine / regulation of respiratory burst involved in inflammatory response / positive regulation of toll-like receptor 2 signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / superoxide-generating NADPH oxidase activator activity / phagolysosome / superoxide-generating NAD(P)H oxidase activity / positive regulation of epidermal growth factor-activated receptor activity ... smooth muscle hypertrophy / reactive oxygen species biosynthetic process / cellular response to L-glutamine / regulation of respiratory burst involved in inflammatory response / positive regulation of toll-like receptor 2 signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / superoxide-generating NADPH oxidase activator activity / phagolysosome / superoxide-generating NAD(P)H oxidase activity / positive regulation of epidermal growth factor-activated receptor activity / positive regulation of defense response to bacterium / mucus secretion / Cross-presentation of particulate exogenous antigens (phagosomes) / perinuclear endoplasmic reticulum / cytochrome complex assembly / NADPH oxidase complex / WNT5:FZD7-mediated leishmania damping / respiratory burst / cellular response to testosterone stimulus / regulation of release of sequestered calcium ion into cytosol / ROS and RNS production in phagocytes / phosphatidylinositol-3,4-bisphosphate binding / cellular response to ethanol / 酸化還元酵素 / superoxide anion generation / response to angiotensin / hydrogen peroxide biosynthetic process / protein targeting to membrane / positive regulation of mucus secretion / positive regulation of p38MAPK cascade / positive regulation of reactive oxygen species biosynthetic process / monoatomic ion channel complex / response to aldosterone / small GTPase-mediated signal transduction / superoxide metabolic process / Detoxification of Reactive Oxygen Species / tertiary granule membrane / RHO GTPases Activate NADPH Oxidases / RAC2 GTPase cycle / RAC3 GTPase cycle / cellular defense response / specific granule membrane / positive regulation of phagocytosis / monoatomic ion transmembrane transport / RAC1 GTPase cycle / cellular response to cadmium ion / phosphatidylinositol binding / response to nutrient / secretory granule / establishment of localization in cell / cellular response to glucose stimulus / positive regulation of JNK cascade / cytoplasmic side of plasma membrane / defense response / VEGFA-VEGFR2 Pathway / cellular response to reactive oxygen species / SH3 domain binding / phagocytic vesicle membrane / positive regulation of angiogenesis / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / nuclear envelope / flavin adenine dinucleotide binding / oxidoreductase activity / electron transfer activity / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / endosome / response to xenobiotic stimulus / inflammatory response / protein heterodimerization activity / innate immune response / GTPase activity / neuronal cell body / dendrite / heme binding / Neutrophil degranulation / endoplasmic reticulum membrane / GTP binding / positive regulation of DNA-templated transcription / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 Cytochrome b245, heavy chain / Cytochrome b558 alpha-subunit / Cytochrome Cytochrome b558 alpha-subunit / Neutrophil cytosol factor 1 / Neutrophil cytosol factor 1, C-terminal / Neutrophil cytosol factor 1, PBR/AIR / Neutrophil cytosol factor 1, PX domain / Neutrophil cytosol factor 1, first SH3 domain / Neutrophil cytosol factor 1, second SH3 domain / NADPH oxidase subunit p47Phox, C terminal domain ... Cytochrome b245, heavy chain / Cytochrome b558 alpha-subunit / Cytochrome Cytochrome b558 alpha-subunit / Neutrophil cytosol factor 1 / Neutrophil cytosol factor 1, C-terminal / Neutrophil cytosol factor 1, PBR/AIR / Neutrophil cytosol factor 1, PX domain / Neutrophil cytosol factor 1, first SH3 domain / Neutrophil cytosol factor 1, second SH3 domain / NADPH oxidase subunit p47Phox, C terminal domain / Neutrophil cytosol factor 1, PBR/AIR / Ferric reductase, NAD binding domain / Ferric reductase NAD binding domain / FAD-binding 8 / FAD-binding domain / Ferric reductase transmembrane component-like domain / Ferric reductase like transmembrane component / PhoX homologous domain, present in p47phox and p40phox. / PX domain profile. / PX domain / Phox homology / PX domain superfamily / small GTPase Rab1 family profile. / Small GTPase Rho / small GTPase Rho family profile. / small GTPase Ras family profile. / FAD-binding domain, ferredoxin reductase-type / Ferredoxin-NADP reductase (FNR), nucleotide-binding domain / Ferredoxin reductase-type FAD binding domain profile. / Riboflavin synthase-like beta-barrel / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / SH3 domain / Small GTPase / Ras family / Rab subfamily of small GTPases / Src homology 3 domains / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Small GTP-binding protein domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 : / Rac family small GTPase 1 / Cytochrome b-245 heavy chain / Cytochrome b-245 light chain / Neutrophil cytosol factor 1 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 : 2.79 Å 詳細 データ登録者Chen L / Liu X 資金援助 中国, 3件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 31821091 中国 Ministry of Science and Technology (MoST, China) 2022YFA1303000 中国 National Natural Science Foundation of China (NSFC) 32225027 中国
引用ジャーナル : Nature / 年 : 2024タイトル : Structure of human phagocyte NADPH oxidase in the activated state.著者 : Xiaoyu Liu / Yiting Shi / Rui Liu / Kangcheng Song / Lei Chen / 要旨 : Phagocyte NADPH oxidase, a protein complex with a core made up of NOX2 and p22 subunits, is responsible for transferring electrons from intracellular NADPH to extracellular oxygen. This process ... Phagocyte NADPH oxidase, a protein complex with a core made up of NOX2 and p22 subunits, is responsible for transferring electrons from intracellular NADPH to extracellular oxygen. This process generates superoxide anions that are vital for killing pathogens. The activation of phagocyte NADPH oxidase requires membrane translocation and the binding of several cytosolic factors. However, the exact mechanism by which cytosolic factors bind to and activate NOX2 is not well understood. Here we present the structure of the human NOX2-p22 complex activated by fragments of three cytosolic factors: p47, p67 and Rac1. The structure reveals that the p67-Rac1 complex clamps onto the dehydrogenase domain of NOX2 and induces its contraction, which stabilizes the binding of NADPH and results in a reduction of the distance between the NADPH-binding domain and the flavin adenine dinucleotide (FAD)-binding domain. Furthermore, the dehydrogenase domain docks onto the bottom of the transmembrane domain of NOX2, which reduces the distance between FAD and the inner haem. These structural rearrangements might facilitate the efficient transfer of electrons between the redox centres in NOX2 and lead to the activation of phagocyte NADPH oxidase. 履歴 登録 2023年9月18日 - ヘッダ(付随情報) 公開 2024年1月24日 - マップ公開 2024年1月24日 - 更新 2024年3月20日 - 現状 2024年3月20日 処理サイト : PDBj / 状態 : 公開
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