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| - | [[Image:1oey.jpg|left|200px]]<br /><applet load="1oey" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1oey, resolution 2.00Å" /> | |
| - | '''HETERODIMER OF P40PHOX AND P67PHOX PB1 DOMAINS FROM HUMAN NADPH OXIDASE'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Heterodimer of p40phox and p67phox PB1 domains from human NADPH oxidase== |
| - | Maximal activation of NADPH oxidase requires formation of a complex, between the p40(phox) and p67(phox) subunits via association of their PB1, domains. We have determined the crystal structure of the, p40(phox)/p67(phox) PB1 heterodimer, which reveals that both domains have, a beta grasp topology and that they bind in a front-to-back arrangement, through conserved electrostatic interactions between an acidic OPCA motif, on p40(phox) and basic residues in p67(phox). The structure enabled us to, identify residues critical for heterodimerization among other members of, the PB1 domain family, including the atypical protein kinase C zeta (PKC, zeta) and its partners Par6 and p62 (ZIP, sequestosome). Both Par6 and p62, use their basic "back" to interact with the OPCA motif on the "front" of, the PKC zeta. Besides heterodimeric interactions, some PB1 domains, like, the p62 PB1, can make homotypic front-to-back arrays.
| + | <StructureSection load='1oey' size='340' side='right'caption='[[1oey]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1oey]] is a 8 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=1OEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OEY FirstGlance]. <br> |
| | + | </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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1oey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oey OCA], [https://pdbe.org/1oey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oey RCSB], [https://www.ebi.ac.uk/pdbsum/1oey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oey ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/NCF2_HUMAN NCF2_HUMAN] Defects in NCF2 are a cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 2 (CGD2) [MIM:[https://omim.org/entry/233710 233710]. Chronic granulomatous disease is a genetically heterogeneous 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:8286749</ref> <ref>PMID:9070911</ref> <ref>PMID:10498624</ref> <ref>PMID:10598813</ref> <ref>PMID:11112388</ref> <ref>PMID:16937026</ref> <ref>PMID:18625437</ref> <ref>PMID:19624736</ref> <ref>PMID:20167518</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NCF2_HUMAN NCF2_HUMAN] NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oe/1oey_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1oey ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==Disease== | + | ==See Also== |
| - | Known disease associated with this structure: Chronic granulomatous disease due to deficiency of NCF-2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608515 608515]]
| + | *[[NADPH oxidase 3D structures|NADPH oxidase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | 1OEY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OEY OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | |
| - | PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62., Wilson MI, Gill DJ, Perisic O, Quinn MT, Williams RL, Mol Cell. 2003 Jul;12(1):39-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12887891 12887891]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Gill, D.J.]] | + | [[Category: Gill DJ]] |
| - | [[Category: Perisic, O.]] | + | [[Category: Perisic O]] |
| - | [[Category: Quinn, M.T.]] | + | [[Category: Quinn MT]] |
| - | [[Category: Williams, R.L.]] | + | [[Category: Williams RL]] |
| - | [[Category: Wilson, M.I.]] | + | [[Category: Wilson MI]] |
| - | [[Category: heterodimerization]]
| + | |
| - | [[Category: nadph oxidase]]
| + | |
| - | [[Category: pb1 domain]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:34:09 2008''
| + | |
| Structural highlights
Disease
NCF2_HUMAN Defects in NCF2 are a cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 2 (CGD2) [MIM:233710. Chronic granulomatous disease is a genetically heterogeneous 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] [2] [3] [4] [5] [6] [7] [8] [9]
Function
NCF2_HUMAN NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ de Boer M, Hilarius-Stokman PM, Hossle JP, Verhoeven AJ, Graf N, Kenney RT, Seger R, Roos D. Autosomal recessive chronic granulomatous disease with absence of the 67-kD cytosolic NADPH oxidase component: identification of mutation and detection of carriers. Blood. 1994 Jan 15;83(2):531-6. PMID:8286749
- ↑ Bonizzato A, Russo MP, Donini M, Dusi S. Identification of a double mutation (D160V-K161E) in the p67phox gene of a chronic granulomatous disease patient. Biochem Biophys Res Commun. 1997 Feb 24;231(3):861-3. PMID:9070911 doi:S0006-291X(97)96204-5
- ↑ Patino PJ, Rae J, Noack D, Erickson R, Ding J, de Olarte DG, Curnutte JT. Molecular characterization of autosomal recessive chronic granulomatous disease caused by a defect of the nicotinamide adenine dinucleotide phosphate (reduced form) oxidase component p67-phox. Blood. 1999 Oct 1;94(7):2505-14. PMID:10498624
- ↑ Noack D, Rae J, Cross AR, Munoz J, Salmen S, Mendoza JA, Rossi N, Curnutte JT, Heyworth PG. Autosomal recessive chronic granulomatous disease caused by novel mutations in NCF-2, the gene encoding the p67-phox component of phagocyte NADPH oxidase. Hum Genet. 1999 Nov;105(5):460-7. PMID:10598813
- ↑ Cross AR, Noack D, Rae J, Curnutte JT, Heyworth PG. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (first update). Blood Cells Mol Dis. 2000 Oct;26(5):561-5. PMID:11112388 doi:10.1006/bcmd.2000.0333
- ↑ El Kares R, Barbouche MR, Elloumi-Zghal H, Bejaoui M, Chemli J, Mellouli F, Tebib N, Abdelmoula MS, Boukthir S, Fitouri Z, M'Rad S, Bouslama K, Touiri H, Abdelhak S, Dellagi MK. Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia. J Hum Genet. 2006;51(10):887-95. Epub 2006 Aug 26. PMID:16937026 doi:10.1007/s10038-006-0039-8
- ↑ Yu G, Hong DK, Dionis KY, Rae J, Heyworth PG, Curnutte JT, Lewis DB. Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive chronic granulomatous disease. Clin Immunol. 2008 Aug;128(2):117-26. doi: 10.1016/j.clim.2008.05.008. PMID:18625437 doi:10.1016/j.clim.2008.05.008
- ↑ Koker MY, Sanal O, van Leeuwen K, de Boer M, Metin A, Patiroglu T, Ozgur TT, Tezcan I, Roos D. Four different NCF2 mutations in six families from Turkey and an overview of NCF2 gene mutations. Eur J Clin Invest. 2009 Oct;39(10):942-51. doi: 10.1111/j.1365-2362.2009.02195.x., Epub 2009 Jul 17. PMID:19624736 doi:10.1111/j.1365-2362.2009.02195.x
- ↑ Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, van Leeuwen K, Koker MY, Wolach B, Roesler J, Malech HL, Holland SM, Gallin JI, Stasia MJ. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010 Apr 15;44(4):291-9. doi: 10.1016/j.bcmd.2010.01.009., Epub 2010 Feb 18. PMID:20167518 doi:10.1016/j.bcmd.2010.01.009
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