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- PDB-8wej: Structure of human phagocyte NADPH oxidase in the activated state -
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Open data
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Basic information
Entry | Database: PDB / ID: 8wej | ||||||||||||
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Title | Structure of human phagocyte NADPH oxidase in the activated state | ||||||||||||
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![]() | OXIDOREDUCTASE / NOX2 / p22 / CYBA / CYBB / TP1170 / NOX / p67 / Rac / p47 | ||||||||||||
Function / homology | ![]() 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 / respiratory burst / WNT5:FZD7-mediated leishmania damping / 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 / Oxidoreductases / 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 / SH3 domain binding / cellular response to reactive oxygen species / 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 Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.79 Å | ||||||||||||
![]() | Chen, L. / Liu, X. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of human phagocyte NADPH oxidase in the activated state. Authors: Xiaoyu Liu / Yiting Shi / Rui Liu / Kangcheng Song / Lei Chen / ![]() Abstract: 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. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Download
PDBx/mmCIF format | ![]() | 268.7 KB | Display | ![]() |
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PDB format | ![]() | 202 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.7 MB | Display | ![]() |
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Full document | ![]() | 1.7 MB | Display | |
Data in XML | ![]() | 53.7 KB | Display | |
Data in CIF | ![]() | 78.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 37477MC ![]() 8x2lC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Cytochrome b-245 ... , 2 types, 2 molecules AB
#1: Protein | Mass: 21005.398 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 65412.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein , 3 types, 3 molecules CDE
#3: Protein | Mass: 32813.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: Protein | Mass: 34978.535 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#5: Protein | Mass: 21463.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Antibody , 2 types, 2 molecules HL
#6: Antibody | Mass: 27603.949 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#7: Antibody | Mass: 26238.188 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Sugars , 2 types, 3 molecules ![](data/chem/img/NAG.gif)
#8: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#10: Sugar |
-Non-polymers , 6 types, 8 molecules ![](data/chem/img/HEM.gif)
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![](data/chem/img/NDP.gif)
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#9: Chemical | #11: Chemical | #12: Chemical | ChemComp-NDP / | #13: Chemical | ChemComp-FDA / | #14: Chemical | ChemComp-GTP / | #15: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: activated NOX2-p22 complex / Type: COMPLEX / Entity ID: #1-#7 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 52 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 2.79 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 209359 / Symmetry type: POINT |