1uec: Difference between revisions
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== | ==Crystal structure of autoinhibited form of tandem SH3 domain of p47phox== | ||
[[http://www.uniprot.org/uniprot/NCF1_HUMAN NCF1_HUMAN | <StructureSection load='1uec' size='340' side='right'caption='[[1uec]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1uec]] is a 1 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=1UEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UEC 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]] 1.82Å</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=1uec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uec OCA], [https://pdbe.org/1uec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uec RCSB], [https://www.ebi.ac.uk/pdbsum/1uec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uec ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/NCF1_HUMAN NCF1_HUMAN] Defects in NCF1 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 1 (CGD1) [MIM:[https://omim.org/entry/233700 233700]. 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:2011585</ref> <ref>PMID:11133775</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NCF1_HUMAN NCF1_HUMAN] NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).<ref>PMID:19801500</ref> | |||
== 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/ue/1uec_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=1uec ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The phagocyte NADPH oxidase is a multisubunit enzyme responsible for the production of reactive oxygen species. p47(phox) is a cytosolic component of the NADPH oxidase and plays an important role in the assembly of the activated complex. The structural determination of the tandem SH3 domains of p47(phox) is crucial for elucidation of the molecular mechanism of the activation of p47(phox). We determined the X-ray crystal structure of the tandem SH3 domains with the polybasic/autoinhibitory region (PBR/AIR) of p47(phox). The GAPPR sequence involved in PBR/AIR forms a left-handed polyproline type-II helix (PPII) and interacts with the conserved SH3 binding surfaces of the SH3 domains simultaneously. These SH3 domains are related by a 2-fold pseudosymmetry axis at the centre of the binding groove and interact with the single PPII helix formed by the GAPPR sequence with opposite orientation. In addition, a number of intra-molecular interactions among the SH3 domains, PBR/AIR and the linker tightly hold the architecture of the tandem SH3 domains into the compact structure and stabilize the autoinhibited form synergistically. Phosphorylation of the serine residues in PBR/AIR could destabilize and successively release the intra-molecular interactions. Thus, the overall structure could be rearranged from the autoinhibitory conformation to the active conformation and the PPII ligand binding surfaces on the SH3 domains are now unmasked, which enables their interaction with the target sequence in p22(phox). | |||
A molecular mechanism for autoinhibition of the tandem SH3 domains of p47phox, the regulatory subunit of the phagocyte NADPH oxidase.,Yuzawa S, Suzuki NN, Fujioka Y, Ogura K, Sumimoto H, Inagaki F Genes Cells. 2004 May;9(5):443-56. PMID:15147273<ref>PMID:15147273</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1uec" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[NADPH oxidase 3D structures|NADPH oxidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Fujioka | [[Category: Large Structures]] | ||
[[Category: Inagaki | [[Category: Fujioka Y]] | ||
[[Category: Ogura | [[Category: Inagaki F]] | ||
[[Category: Sumimoto | [[Category: Ogura K]] | ||
[[Category: Suzuki | [[Category: Sumimoto H]] | ||
[[Category: Yuzawa | [[Category: Suzuki NN]] | ||
[[Category: Yuzawa S]] | |||
Latest revision as of 02:51, 28 December 2023
Crystal structure of autoinhibited form of tandem SH3 domain of p47phoxCrystal structure of autoinhibited form of tandem SH3 domain of p47phox
Structural highlights
DiseaseNCF1_HUMAN Defects in NCF1 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 1 (CGD1) [MIM:233700. 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] FunctionNCF1_HUMAN NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).[3] 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 PubMedThe phagocyte NADPH oxidase is a multisubunit enzyme responsible for the production of reactive oxygen species. p47(phox) is a cytosolic component of the NADPH oxidase and plays an important role in the assembly of the activated complex. The structural determination of the tandem SH3 domains of p47(phox) is crucial for elucidation of the molecular mechanism of the activation of p47(phox). We determined the X-ray crystal structure of the tandem SH3 domains with the polybasic/autoinhibitory region (PBR/AIR) of p47(phox). The GAPPR sequence involved in PBR/AIR forms a left-handed polyproline type-II helix (PPII) and interacts with the conserved SH3 binding surfaces of the SH3 domains simultaneously. These SH3 domains are related by a 2-fold pseudosymmetry axis at the centre of the binding groove and interact with the single PPII helix formed by the GAPPR sequence with opposite orientation. In addition, a number of intra-molecular interactions among the SH3 domains, PBR/AIR and the linker tightly hold the architecture of the tandem SH3 domains into the compact structure and stabilize the autoinhibited form synergistically. Phosphorylation of the serine residues in PBR/AIR could destabilize and successively release the intra-molecular interactions. Thus, the overall structure could be rearranged from the autoinhibitory conformation to the active conformation and the PPII ligand binding surfaces on the SH3 domains are now unmasked, which enables their interaction with the target sequence in p22(phox). A molecular mechanism for autoinhibition of the tandem SH3 domains of p47phox, the regulatory subunit of the phagocyte NADPH oxidase.,Yuzawa S, Suzuki NN, Fujioka Y, Ogura K, Sumimoto H, Inagaki F Genes Cells. 2004 May;9(5):443-56. PMID:15147273[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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