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
negative regulation of glomerular filtration by angiotensin / smooth muscle hypertrophy / superoxide-generating NADPH oxidase activity / 酸化還元酵素; 酸素が電子受容体 / regulation of respiratory burst involved in inflammatory response / neutrophil-mediated killing of gram-positive bacterium / superoxide-generating NADPH oxidase activator activity / positive regulation of mucus secretion / hypoxia-inducible factor-1alpha signaling pathway / cellular response to L-glutamine ... negative regulation of glomerular filtration by angiotensin / smooth muscle hypertrophy / superoxide-generating NADPH oxidase activity / 酸化還元酵素; 酸素が電子受容体 / regulation of respiratory burst involved in inflammatory response / neutrophil-mediated killing of gram-positive bacterium / superoxide-generating NADPH oxidase activator activity / positive regulation of mucus secretion / hypoxia-inducible factor-1alpha signaling pathway / cellular response to L-glutamine / neutrophil-mediated killing of fungus / phagolysosome / positive regulation of toll-like receptor 2 signaling pathway / positive regulation of defense response to bacterium / mucus secretion / perinuclear endoplasmic reticulum / superoxide-generating NAD(P)H oxidase activity / Cross-presentation of particulate exogenous antigens (phagosomes) / leukotriene metabolic process / NADPH oxidase complex / cytochrome complex assembly / response to yeast / cellular response to testosterone stimulus / respiratory burst / WNT5:FZD7-mediated leishmania damping / respiratory burst involved in defense response / response to angiotensin / phosphatidylinositol-3,4-bisphosphate binding / ROS and RNS production in phagocytes / response to aldosterone / regulation of release of sequestered calcium ion into cytosol / hydrogen peroxide biosynthetic process / protein targeting to membrane / superoxide anion generation / small GTPase-mediated signal transduction / superoxide metabolic process / Detoxification of Reactive Oxygen Species / positive regulation of reactive oxygen species biosynthetic process / cellular response to cadmium ion / cellular response to ethanol / tertiary granule membrane / cellular response to angiotensin / RHO GTPases Activate NADPH Oxidases / monoatomic ion channel complex / RAC2 GTPase cycle / RAC3 GTPase cycle / cellular defense response / NADPH binding / specific granule membrane / stress fiber / positive regulation of superoxide anion generation / positive regulation of endothelial cell proliferation / response to nutrient / RAC1 GTPase cycle / positive regulation of smooth muscle cell proliferation / phosphatidylinositol binding / FAD binding / response to interleukin-1 / positive regulation of phagocytosis / secretory granule / epithelial cell proliferation / response to activity / small monomeric GTPase / cellular response to glucose stimulus / response to nutrient levels / establishment of localization in cell / cellular response to mechanical stimulus / cellular response to gamma radiation / defense response / SH3 domain binding / positive regulation of interleukin-6 production / VEGFA-VEGFR2 Pathway / cytoplasmic side of plasma membrane / phagocytic vesicle membrane / positive regulation of angiogenesis / positive regulation of tumor necrosis factor production / cellular response to tumor necrosis factor / nuclear envelope / flavin adenine dinucleotide binding / positive regulation of cell growth / monoatomic ion transmembrane transport / response to hypoxia / electron transfer activity / endosome / apical plasma membrane / inflammatory response / response to xenobiotic stimulus / protein heterodimerization activity / innate immune response / focal adhesion / neuronal cell body / GTPase activity / heme binding / dendrite / endoplasmic reticulum membrane / Neutrophil degranulation / GTP binding / metal ion binding / membrane / plasma membrane 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 Rho / Small GTPase Rab domain profile. / Small GTPase Rho domain profile. / Small GTPase Ras domain 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 / SH3 domain / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / 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 : / small monomeric GTPase / NADPH oxidase 2 / 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10月16日 - 現状 2024年10月16日 処理サイト : PDBj / 状態 : 公開
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