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Yorodumi- PDB-8x2l: Structure of human phagocyte NADPH oxidase in the resting state i... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8x2l | |||||||||||||||
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Title | Structure of human phagocyte NADPH oxidase in the resting state in the presence of 2 mM NADPH | |||||||||||||||
Components |
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Keywords | OXIDOREDUCTASE / NOX2 / p22 / CYBA / CYBB / TP1170 / NOX | |||||||||||||||
Function / homology | Function and homology information smooth muscle hypertrophy / cellular response to L-glutamine / positive regulation of toll-like receptor 2 signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / superoxide-generating NAD(P)H oxidase activity / positive regulation of defense response to bacterium / mucus secretion / Cross-presentation of particulate exogenous antigens (phagosomes) / perinuclear endoplasmic reticulum / cytochrome complex assembly ...smooth muscle hypertrophy / cellular response to L-glutamine / positive regulation of toll-like receptor 2 signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / superoxide-generating NAD(P)H oxidase 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 / regulation of release of sequestered calcium ion into cytosol / ROS and RNS production in phagocytes / cellular response to ethanol / Oxidoreductases / superoxide anion generation / response to angiotensin / hydrogen peroxide biosynthetic process / positive regulation of mucus secretion / positive regulation of reactive oxygen species biosynthetic process / monoatomic ion channel complex / response to aldosterone / superoxide metabolic process / Detoxification of Reactive Oxygen Species / tertiary granule membrane / RHO GTPases Activate NADPH Oxidases / RAC2 GTPase cycle / RAC3 GTPase cycle / specific granule membrane / positive regulation of phagocytosis / monoatomic ion transmembrane transport / RAC1 GTPase cycle / cellular response to cadmium ion / response to nutrient / secretory granule / establishment of localization in cell / defense response / VEGFA-VEGFR2 Pathway / 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 / endosome / response to xenobiotic stimulus / inflammatory response / protein heterodimerization activity / innate immune response / neuronal cell body / dendrite / heme binding / Neutrophil degranulation / endoplasmic reticulum membrane / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.99 Å | |||||||||||||||
Authors | Chen, L. / Liu, X. | |||||||||||||||
Funding support | China, 4items
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Citation | Journal: Nature / Year: 2024 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8x2l.cif.gz | 179.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8x2l.ent.gz | 134.7 KB | Display | PDB format |
PDBx/mmJSON format | 8x2l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8x2l_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8x2l_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8x2l_validation.xml.gz | 42.8 KB | Display | |
Data in CIF | 8x2l_validation.cif.gz | 61.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x2/8x2l ftp://data.pdbj.org/pub/pdb/validation_reports/x2/8x2l | HTTPS FTP |
-Related structure data
Related structure data | 38016MC 8wejC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: CYBA / Production host: Homo sapiens (human) / References: UniProt: P13498 |
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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.) Homo sapiens (human) / Gene: CYBB / Production host: Homo sapiens (human) / References: UniProt: P04839 |
-Antibody , 2 types, 2 molecules HL
#3: Antibody | Mass: 27603.949 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Escherichia coli (E. coli) |
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#4: Antibody | Mass: 26238.188 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Escherichia coli (E. coli) |
-Sugars , 2 types, 3 molecules
#5: 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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#8: Sugar |
-Non-polymers , 4 types, 5 molecules
#6: Chemical | ChemComp-FAD / | ||||
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#7: Chemical | #9: Chemical | ChemComp-MG / | #10: Water | ChemComp-HOH / | |
-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 |
-Sample preparation
Component | Name: resting NOX2-p22 complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
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) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 2.99 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 183394 / Symmetry type: POINT |