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1uec

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Revision as of 13:04, 6 January 2015

Crystal structure of autoinhibited form of tandem SH3 domain of p47phox

Structural highlights

1uec is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[NCF1_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]

Function

[NCF1_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 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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Casimir CM, Bu-Ghanim HN, Rodaway AR, Bentley DL, Rowe P, Segal AW. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2753-7. PMID:2011585
↑ Noack D, Rae J, Cross AR, Ellis BA, Newburger PE, Curnutte JT, Heyworth PG. Autosomal recessive chronic granulomatous disease caused by defects in NCF-1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF-1 pseudogenes. Blood. 2001 Jan 1;97(1):305-11. PMID:11133775
↑ Kilpatrick LE, Sun S, Li H, Vary TC, Korchak HM. Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC. J Leukoc Biol. 2010 Jan;87(1):153-64. doi: 10.1189/jlb.0408230. Epub 2009 Oct 2. PMID:19801500 doi:10.1189/jlb.0408230
↑ Yuzawa S, Suzuki NN, Fujioka Y, Ogura K, Sumimoto H, Inagaki F. A molecular mechanism for autoinhibition of the tandem SH3 domains of p47phox, the regulatory subunit of the phagocyte NADPH oxidase. Genes Cells. 2004 May;9(5):443-56. PMID:15147273 doi:10.1111/j.1356-9597.2004.00733.x

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1uec"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1uec]] is a 1 chain structure with sequence 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=1UEC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UEC FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uec OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1uec RCSB], [http://www.ebi.ac.uk/pdbsum/1uec PDBsum]</span></td></tr>
+</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=1uec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uec OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1uec RCSB], [http://www.ebi.ac.uk/pdbsum/1uec PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://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:[http://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>
@@ Line 32: / Line 32: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Fujioka, Y.]]
+[[Category: Fujioka, Y]]
-[[Category: Inagaki, F.]]
+[[Category: Inagaki, F]]
-[[Category: Ogura, K.]]
+[[Category: Ogura, K]]
-[[Category: Sumimoto, H.]]
+[[Category: Sumimoto, H]]
-[[Category: Suzuki, N N.]]
+[[Category: Suzuki, N N]]
-[[Category: Yuzawa, S.]]
+[[Category: Yuzawa, S]]
 [[Category: Autoinhibition]]
 [[Category: Nadph oxidase]]

1uec

From Proteopedia

Revision as of 13:04, 6 January 2015

Crystal structure of autoinhibited form of tandem SH3 domain of p47phox

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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