7u8g

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Current revision (09:14, 17 October 2024) (edit) (undo)
 
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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7u8g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U8G FirstGlance]. <br>
<table><tr><td colspan='2'>[[7u8g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U8G FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u8g OCA], [https://pdbe.org/7u8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u8g RCSB], [https://www.ebi.ac.uk/pdbsum/7u8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u8g ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u8g OCA], [https://pdbe.org/7u8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u8g RCSB], [https://www.ebi.ac.uk/pdbsum/7u8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u8g ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[https://www.uniprot.org/uniprot/CY24B_HUMAN CY24B_HUMAN] Defects in CYBB are a cause of granulomatous disease,chronic, X-linked (CGD) [MIM:[https://omim.org/entry/306400 306400]. A disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.<ref>PMID:12139950</ref> <ref>PMID:2556453</ref> <ref>PMID:1710153</ref> <ref>PMID:8101486</ref> <ref>PMID:7927345</ref> <ref>PMID:8182143</ref> <ref>PMID:8916969</ref> <ref>PMID:9111587</ref> <ref>PMID:9585602</ref> <ref>PMID:9856476</ref> <ref>PMID:9794433</ref> <ref>PMID:9667376</ref> <ref>PMID:10089913</ref> <ref>PMID:9888386</ref> <ref>PMID:10914676</ref> <ref>PMID:11462241</ref> <ref>PMID:11997083</ref> <ref>PMID:15338276</ref> <ref>PMID:18773283</ref> <ref>PMID:22125116</ref> Defects in CYBB are a cause of mycobacteriosis atypical X-linked type 2 (AMCBX2) [MIM:[https://omim.org/entry/300645 300645]. A rare condition characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections.<ref>PMID:21278736</ref>
 
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== Function ==
 
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[https://www.uniprot.org/uniprot/CY24B_HUMAN CY24B_HUMAN] Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.[https://www.uniprot.org/uniprot/A0A6M5E0N3_ADE02 A0A6M5E0N3_ADE02]
 
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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NOX2 is the prototypical member of the NADPH oxidase NOX superfamily and produces superoxide (O2(*-)), a key reactive oxygen species (ROS) that is essential in innate and adaptive immunity. Mutations that lead to deficiency in NOX2 activity correlate with increased susceptibility to bacterial and fungal infections, resulting in chronic granulomatous disease. The core of NOX2 is formed by a heterodimeric transmembrane complex composed of NOX2 (formerly gp91) and p22, but a detailed description of its structural architecture is lacking. Here, we present the structure of the human NOX2 core complex bound to a selective anti-NOX2 antibody fragment. The core complex reveals an intricate extracellular topology of NOX2, a four-transmembrane fold of the p22 subunit, and an extensive transmembrane interface which provides insights into NOX2 assembly and activation. Functional assays uncover an inhibitory activity of the 7G5 antibody mediated by internalization-dependent and internalization-independent mechanisms. Overall, our results provide insights into the NOX2 core complex architecture, disease-causing mutations, and potential avenues for selective NOX2 pharmacological modulation.
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NOX2 is the prototypical member of the NADPH oxidase NOX superfamily and produces superoxide (O(2)(*-)), a key reactive oxygen species (ROS) that is essential in innate and adaptive immunity. Mutations that lead to deficiency in NOX2 activity correlate with increased susceptibility to bacterial and fungal infections, resulting in chronic granulomatous disease. The core of NOX2 is formed by a heterodimeric transmembrane complex composed of NOX2 (formerly gp91) and p22, but a detailed description of its structural architecture is lacking. Here, we present the structure of the human NOX2 core complex bound to a selective anti-NOX2 antibody fragment. The core complex reveals an intricate extracellular topology of NOX2, a four-transmembrane fold of the p22 subunit, and an extensive transmembrane interface which provides insights into NOX2 assembly and activation. Functional assays uncover an inhibitory activity of the 7G5 antibody mediated by internalization-dependent and internalization-independent mechanisms. Overall, our results provide insights into the NOX2 core complex architecture, disease-causing mutations, and potential avenues for selective NOX2 pharmacological modulation.
Structure of the core human NADPH oxidase NOX2.,Noreng S, Ota N, Sun Y, Ho H, Johnson M, Arthur CP, Schneider K, Lehoux I, Davies CW, Mortara K, Wong K, Seshasayee D, Masureel M, Payandeh J, Yi T, Koerber JT Nat Commun. 2022 Oct 14;13(1):6079. doi: 10.1038/s41467-022-33711-0. PMID:36241643<ref>PMID:36241643</ref>
Structure of the core human NADPH oxidase NOX2.,Noreng S, Ota N, Sun Y, Ho H, Johnson M, Arthur CP, Schneider K, Lehoux I, Davies CW, Mortara K, Wong K, Seshasayee D, Masureel M, Payandeh J, Yi T, Koerber JT Nat Commun. 2022 Oct 14;13(1):6079. doi: 10.1038/s41467-022-33711-0. PMID:36241643<ref>PMID:36241643</ref>

Current revision

Cryo-EM structure of the core human NADPH oxidase NOX2

PDB ID 7u8g

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