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| | <StructureSection load='1w6x' size='340' side='right'caption='[[1w6x]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1w6x' size='340' side='right'caption='[[1w6x]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w6x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W6X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W6X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w6x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W6X FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h6h|1h6h]], [[1oey|1oey]], [[1w70|1w70]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w6x OCA], [http://pdbe.org/1w6x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w6x RCSB], [http://www.ebi.ac.uk/pdbsum/1w6x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w6x 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=1w6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w6x OCA], [https://pdbe.org/1w6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w6x RCSB], [https://www.ebi.ac.uk/pdbsum/1w6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w6x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/NCF4_HUMAN NCF4_HUMAN] Defects in NCF4 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 3 (CGD3) [MIM:[https://omim.org/entry/613960 613960]. CGD3 is 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:19692703</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NCF4_HUMAN NCF4_HUMAN] Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1w6x" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1w6x" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[NADPH oxidase 3D structures|NADPH oxidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brandolin, G]] | + | [[Category: Brandolin G]] |
| - | [[Category: Chenavas, S]] | + | [[Category: Chenavas S]] |
| - | [[Category: Cohen-Addad, C]] | + | [[Category: Cohen-Addad C]] |
| - | [[Category: Dagher, M C]] | + | [[Category: Dagher M-C]] |
| - | [[Category: Fieschi, F]] | + | [[Category: Fieschi F]] |
| - | [[Category: Massenet, C]] | + | [[Category: Massenet C]] |
| - | [[Category: Pebay-Peyroula, E]] | + | [[Category: Pebay-Peyroula E]] |
| - | [[Category: Nadph oxidase]]
| + | |
| - | [[Category: P40phox]]
| + | |
| - | [[Category: Phagocyte]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| Structural highlights
Disease
NCF4_HUMAN Defects in NCF4 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 3 (CGD3) [MIM:613960. CGD3 is 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.[1]
Function
NCF4_HUMAN Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The neutrophil NADPH oxidase produces superoxide anions in response to infection. This reaction is activated by association of cytosolic factors, p47phox and p67phox, and a small G protein Rac with the membranous flavocytochrome b558. Another cytosolic factor, p40phox, is associated to the complex and is reported to play regulatory roles. Initiation of the NADPH oxidase activation cascade has been reported as consecutive to phosphorylation on serines 359/370 and 379 of the p47phox C terminus. These serines surround a polyproline motif that can interact with the Src homology 3 (SH3) module of p40phox (SH3p40) or the C-terminal SH3 of p67phox (C-SH3p67). The latter one presents a higher affinity in the resting state for p47phox. A change in SH3 binding preference following phosphorylation has been postulated earlier. Here we report the crystal structures of SH3p40 alone or in complex with a 12-residue proline-rich region of p47phox at 1.46 angstrom resolution. Using intrinsic tryptophan fluorescence measurements, we compared the affinity of the strict polyproline motif and the whole C terminus peptide with both SH3p40 and C-SH3p67. These data reveal that SH3p40 can interact with a consensus polyproline motif but also with a noncanonical motif of the p47phox C terminus. The electrostatic surfaces of both SH3 are very different, and therefore the binding preference for C-SH3p67 can be attributed to the polyproline motif recognition and particularly to the Arg-368p47 binding mode. The noncanonical motif contributes equally to interaction with both SH3. The influence of serine phosphorylation on residues 359/370 and 379 on the affinity for both SH3 domains has been checked. We conclude that contrarily to previous suggestions, phosphorylation of Ser-359/370 does not modify the SH3 binding affinity for both SH3, whereas phosphorylation of Ser-379 has a destabilizing effect on both interactions. Other mechanisms than a phosphorylation induced switch between the two SH3 must therefore take place for NADPH oxidase activation cascade to start.
Effects of p47phox C terminus phosphorylations on binding interactions with p40phox and p67phox. Structural and functional comparison of p40phox and p67phox SH3 domains.,Massenet C, Chenavas S, Cohen-Addad C, Dagher MC, Brandolin G, Pebay-Peyroula E, Fieschi F J Biol Chem. 2005 Apr 8;280(14):13752-61. Epub 2005 Jan 18. PMID:15657040[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, Marchal CC, Stull ND, Lewis DB, Steele M, Kellner JD, Yu W, Meroueh SO, Nauseef WM, Dinauer MC. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009 Oct 8;114(15):3309-15. doi: 10.1182/blood-2009-07-231498. Epub 2009, Aug 19. PMID:19692703 doi:10.1182/blood-2009-07-231498
- ↑ Massenet C, Chenavas S, Cohen-Addad C, Dagher MC, Brandolin G, Pebay-Peyroula E, Fieschi F. Effects of p47phox C terminus phosphorylations on binding interactions with p40phox and p67phox. Structural and functional comparison of p40phox and p67phox SH3 domains. J Biol Chem. 2005 Apr 8;280(14):13752-61. Epub 2005 Jan 18. PMID:15657040 doi:10.1074/jbc.M412897200
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