+Open data
-Basic information
Entry | Database: PDB / ID: 8gz3 | ||||||||||||
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Title | Structure of human phagocyte NADPH oxidase in the resting state | ||||||||||||
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 / Oxidoreductases / superoxide anion generation / cellular response to ethanol / response to angiotensin / hydrogen peroxide biosynthetic process / positive regulation of mucus secretion / monoatomic ion channel complex / positive regulation of reactive oxygen species biosynthetic process / 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 / cellular response to cadmium ion / RAC1 GTPase cycle / response to nutrient / secretory granule / establishment of localization in cell / defense response / VEGFA-VEGFR2 Pathway / SH3 domain binding / positive regulation of interleukin-6 production / phagocytic vesicle membrane / positive regulation of angiogenesis / positive regulation of tumor necrosis factor production / nuclear envelope / flavin adenine dinucleotide binding / electron transfer activity / oxidoreductase 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) Vicugna pacos (alpaca) Mus musculus (house mouse) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Chen, L. / Liu, R. | ||||||||||||
Funding support | China, 3items
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Citation | Journal: Elife / Year: 2022 Title: Structure of human phagocyte NADPH oxidase in the resting state. Authors: Rui Liu / Kangcheng Song / Jing-Xiang Wu / Xiao-Peng Geng / Liming Zheng / Xiaoyin Gao / Hailin Peng / Lei Chen / Abstract: Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that ...Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8gz3.cif.gz | 227.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8gz3.ent.gz | 176.3 KB | Display | PDB format |
PDBx/mmJSON format | 8gz3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gz/8gz3 ftp://data.pdbj.org/pub/pdb/validation_reports/gz/8gz3 | HTTPS FTP |
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-Related structure data
Related structure data | 34389MC 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, NOX2 / Production host: Homo sapiens (human) / References: UniProt: P04839, Oxidoreductases |
-Antibody , 3 types, 3 molecules LHN
#3: Antibody | Mass: 17975.100 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Fab cleaved from monoclonal antibody purchased from commercial supplier. The expression system is not known. Source: (natural) Mus musculus (house mouse) |
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#4: Antibody | Mass: 18315.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Fab cleaved from monoclonal antibody purchased from commercial supplier. The expression system is not known. Source: (natural) Mus musculus (house mouse) |
#5: Antibody | Mass: 46217.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Escherichia coli (E. coli) |
-Sugars , 2 types, 3 molecules
#6: 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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#9: Sugar |
-Non-polymers , 4 types, 5 molecules
#7: Chemical | ChemComp-FAD / | ||||
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#8: Chemical | #10: Chemical | ChemComp-LBN / | #11: 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: NADPH oxidase2 / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
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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: 2000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 37.6 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 84035 / Symmetry type: POINT |
Refinement | Highest resolution: 3.3 Å |