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PDBsum entry 1wlp

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protein Protein-protein interface(s) links
Oxidoreductase/signaling protein PDB id
1wlp
Jmol
Contents
Protein chains
25 a.a.
138 a.a. *
* Residue conservation analysis
PDB id:
1wlp
Name: Oxidoreductase/signaling protein
Title: Solution structure of the p22phox-p47phox complex
Structure: Cytochrome b-245 light chain. Chain: a. Fragment: alpha polypeptide (1-25). Synonym: flavocytochrome b558, p22phox. Engineered: yes. Neutrophil cytosol factor 1. Chain: b. Fragment: tandem sh3 domain. Synonym: p47phox.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 1 models
Authors: K.Ogura,S.Torikai,K.Saikawa,S.Yuzawa,H.Sumimoto,F.Inagaki
Key ref:
K.Ogura et al. (2006). NMR solution structure of the tandem Src homology 3 domains of p47phox complexed with a p22phox-derived proline-rich peptide. J Biol Chem, 281, 3660-3668. PubMed id: 16326715 DOI: 10.1074/jbc.M505193200
Date:
29-Jun-04     Release date:   04-Oct-05    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13498  (CY24A_HUMAN) -  Cytochrome b-245 light chain
Seq:
Struc:
195 a.a.
25 a.a.*
Protein chain
Pfam   ArchSchema ?
P14598  (NCF1_HUMAN) -  Neutrophil cytosol factor 1
Seq:
Struc:
390 a.a.
138 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biochemical function     superoxide-generating NADPH oxidase activity     1 term  

 

 
DOI no: 10.1074/jbc.M505193200 J Biol Chem 281:3660-3668 (2006)
PubMed id: 16326715  
 
 
NMR solution structure of the tandem Src homology 3 domains of p47phox complexed with a p22phox-derived proline-rich peptide.
K.Ogura, I.Nobuhisa, S.Yuzawa, R.Takeya, S.Torikai, K.Saikawa, H.Sumimoto, F.Inagaki.
 
  ABSTRACT  
 
The phagocyte NADPH oxidase plays a crucial role in host defense against microbial infections by generating reactive oxygen species. It is a multisubunit enzyme composed of membrane-bound flavocytochrome b558 as well as cytosolic components, including p47phox, which is essential for assembly of the complex. When phagocytes are activated, the cytosolic components of the NADPH oxidase translocate to flavocytochrome b558 due to binding of the tandem Src homology 3 (SH3) domains of p47phox to a proline-rich region in p22phox, a subunit of flavocytochrome b558. Using NMR titration, we first identified the proline-rich region of p22phox that is essential for binding to the tandem SH3 domains of p47phox. We subsequently determined the solution structure of the p47phox tandem SH3 domains complexed with the proline-rich peptide of p22phox using NMR spectroscopy. In contrast to the intertwined dimer reported for the crystal state, the solution structure is a monomer. The central region of the p22phox peptide forms a polyproline type II helix that is sandwiched by the N- and C-terminal SH3 domains, as was observed in the crystal structure, whereas the C-terminal region of the peptide takes on a short alpha-helical conformation that provides an additional binding site with the N-terminal SH3 domain. Thus, the C-terminal alpha-helical region of the p22phox peptide increases the binding affinity for the tandem SH3 domains of p47phox more than 10-fold.
 
  Selected figure(s)  
 
Figure 5.
FIGURE 5. Recognition of p22^phox-(149-168) by p47^phox-(151-286). N-SH3, linker, C-SH3 (in ribbon model), and p22^phox-(149-168) (in wire model) are colored blue, orange, green, and red, respectively. a, recognition of p22^phox-(149-168) by N-SH3. b, recognition of p22^phox-(149-168) by C-SH3. The side chains of the N- and C-SH3 domains that recognize p22^phox-(149-168) are also shown as a wire model.
Figure 7.
FIGURE 7. Comparison of the molecular contacts between the structures of the activated and the autoinhibited forms of p47^phox. a, activated form. b, autoinhibited form. The ligand peptide and the autoinhibited region in PBR are shown in pink. For N- and C-SH3 domains, the side chains that participate in the interaction are shown in blue and green, respectively.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 3660-3668) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21213045 G.M.Simonyan, K.A.Galoian, R.M.Simonyan, M.A.Simonyan, and A.A.Galoyan (2011).
Proline Rich Polypeptide (PRP-1) Increases the Superoxide-Producing and Ferrihemoglobin Reducing Activities of Cytochrome B(558) Isoforms from Human Lymphosarcoma Tissue Cells.
  Neurochem Res, 36, 739-745.  
20949063 A.X.Song, C.J.Zhou, Y.Peng, X.C.Gao, Z.R.Zhou, Q.S.Fu, J.Hong, D.H.Lin, and H.Y.Hu (2010).
Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains.
  PLoS One, 5, e13202.  
20930476 F.Inagaki, and F.Inagaki (2010).
[On the occasion of retirement from Graduate School of Pharmaceutical Sciences, Hokkaido University].
  Yakugaku Zasshi, 130, 1251-1262.  
19590096 E.J.Stollar, B.Garcia, P.A.Chong, A.Rath, H.Lin, J.D.Forman-Kay, and A.R.Davidson (2009).
Structural, functional, and bioinformatic studies demonstrate the crucial role of an extended peptide binding site for the SH3 domain of yeast Abp1p.
  J Biol Chem, 284, 26918-26927.
PDB code: 2rpn
19663600 M.A.Jakobsen, S.S.Pedersen, and T.Barington (2009).
Detection of non-DeltaGT NCF-1 mutations in chronic granulomatous disease.
  Genet Test Mol Biomarkers, 13, 505-510.  
18513324 H.Sumimoto (2008).
Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species.
  FEBS J, 275, 3249-3277.  
18422995 S.Teimourian, E.Zomorodian, M.Badalzadeh, A.Pouya, C.Kannengiesser, D.Mansouri, T.Cheraghi, and N.Parvaneh (2008).
Characterization of six novel mutations in CYBA: the gene causing autosomal recessive chronic granulomatous disease.
  Br J Haematol, 141, 848-851.  
18711001 W.Tian, X.J.Li, N.D.Stull, W.Ming, C.I.Suh, S.A.Bissonnette, M.B.Yaffe, S.Grinstein, S.J.Atkinson, and M.C.Dinauer (2008).
Fc{gamma}R-stimulated activation of the NADPH oxidase: phosphoinositide-binding protein p40phox regulates NADPH oxidase activity after enzyme assembly on the phagosome.
  Blood, 112, 3867-3877.  
17602947 J.D.Lambeth, T.Kawahara, and B.Diebold (2007).
Regulation of Nox and Duox enzymatic activity and expression.
  Free Radic Biol Med, 43, 319-331.  
17521420 J.L.Jiménez, B.Hegemann, J.R.Hutchins, J.M.Peters, and R.Durbin (2007).
A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database.
  Genome Biol, 8, R90.  
17900370 T.Kawahara, and J.D.Lambeth (2007).
Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes.
  BMC Evol Biol, 7, 178.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.