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PDBsum entry 1e96

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protein ligands metals Protein-protein interface(s) links
Signaling protein PDB id
1e96
Jmol
Contents
Protein chains
178 a.a. *
185 a.a. *
Ligands
GTP
Metals
_MG
Waters ×77
* Residue conservation analysis
PDB id:
1e96
Name: Signaling protein
Title: Structure of the rac/p67phox complex
Structure: Ras-related c3 botulinum toxin substrate 1. Chain: a. Synonym: rac1. Engineered: yes. Mutation: yes. Neutrophil cytosol factor 2 (ncf-2) tpr domain, residues 1-203. Chain: b. Fragment: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Hetero-Dimer (from PDB file)
Resolution:
2.4Å     R-factor:   0.248     R-free:   0.284
Authors: K.Lapouge,S.J.M.Smith,P.A.Walker,S.J.Gamblin,S.J.Smerdon, K.Rittinger
Key ref: K.Lapouge et al. (2000). Structure of the TPR domain of p67phox in complex with Rac.GTP. Mol Cell, 6, 899-907. PubMed id: 11090627
Date:
10-Oct-00     Release date:   17-Nov-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P63000  (RAC1_HUMAN) -  Ras-related C3 botulinum toxin substrate 1
Seq:
Struc:
192 a.a.
178 a.a.*
Protein chain
Pfam   ArchSchema ?
P19878  (NCF2_HUMAN) -  Neutrophil cytosol factor 2
Seq:
Struc:
 
Seq:
Struc:
526 a.a.
185 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   18 terms 
  Biological process     epithelial cell morphogenesis   68 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
Mol Cell 6:899-907 (2000)
PubMed id: 11090627  
 
 
Structure of the TPR domain of p67phox in complex with Rac.GTP.
K.Lapouge, S.J.Smith, P.A.Walker, S.J.Gamblin, S.J.Smerdon, K.Rittinger.
 
  ABSTRACT  
 
p67phox is an essential part of the NADPH oxidase, a multiprotein enzyme complex that produces superoxide ions in response to microbial infection. Binding of the small GTPase Rac to p67phox is a key step in the assembly of the active enzyme complex. The structure of Rac.GTP bound to the N-terminal TPR (tetratricopeptide repeat) domain of p67phox reveals a novel mode of Rho family/effector interaction and explains the basis of GTPase specificity. Complex formation is largely mediated by an insertion between two TPR motifs, suggesting an unsuspected versatility of TPR domains in target recognition and in their more general role as scaffolds for the assembly of multiprotein complexes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20842512 B.Yu, Y.Chen, Q.Wu, P.Li, Y.Shao, J.Zhang, Q.Zhong, X.Peng, H.Yang, X.Hu, B.Chen, M.Guan, J.Wan, and W.Zhang (2011).
The association between single-nucleotide polymorphisms of NCF2 and systemic lupus erythematosus in Chinese mainland population.
  Clin Rheumatol, 30, 521-527.  
19948726 A.Chatterjee, L.Wang, D.L.Armstrong, and S.Rossie (2010).
Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro.
  J Biol Chem, 285, 3872-3882.  
20506260 A.D.Wilkins, R.Lua, S.Erdin, R.M.Ward, and O.Lichtarge (2010).
Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation.
  Protein Sci, 19, 1296-1311.  
20637895 D.Shao, A.W.Segal, and L.V.Dekker (2010).
Subcellular localisation of the p40phox component of NADPH oxidase involves direct interactions between the Phox homology domain and F-actin.
  Int J Biochem Cell Biol, 42, 1736-1743.  
20813901 K.E.Anderson, T.A.Chessa, K.Davidson, R.B.Henderson, S.Walker, T.Tolmachova, K.Grys, O.Rausch, M.C.Seabra, V.L.Tybulewicz, L.R.Stephens, and P.T.Hawkins (2010).
PtdIns3P and Rac direct the assembly of the NADPH oxidase on a novel, pre-phagosomal compartment during FcR-mediated phagocytosis in primary mouse neutrophils.
  Blood, 116, 4978-4989.  
20861461 T.A.Chessa, K.E.Anderson, Y.Hu, Q.Xu, O.Rausch, L.R.Stephens, and P.T.Hawkins (2010).
Phosphorylation of threonine 154 in p40phox is an important physiological signal for activation of the neutrophil NADPH oxidase.
  Blood, 116, 6027-6036.  
19864426 T.Oda, H.Hashimoto, N.Kuwabara, S.Akashi, K.Hayashi, C.Kojima, H.L.Wong, T.Kawasaki, K.Shimamoto, M.Sato, and T.Shimizu (2010).
Structure of the N-terminal regulatory domain of a plant NADPH oxidase and its functional implications.
  J Biol Chem, 285, 1435-1445.
PDB code: 3a8r
19358632 G.M.Bokoch, B.Diebold, J.S.Kim, and D.Gianni (2009).
Emerging evidence for the importance of phosphorylation in the regulation of NADPH oxidases.
  Antioxid Redox Signal, 11, 2429-2441.  
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Structure of a SusD homologue, BT1043, involved in mucin O-glycan utilization in a prominent human gut symbiont.
  Biochemistry, 48, 1532-1542.
PDB codes: 3ehm 3ehn
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Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide.
  Protein Sci, 18, 2115-2124.
PDB code: 2fbn
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NoxA activation by the small GTPase RacA is required to maintain a mutualistic symbiotic association between Epichloë festucae and perennial ryegrass.
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Myxococcus-from single-cell polarity to complex multicellular patterns.
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Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species.
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Reactive oxygen species in phagocytic leukocytes.
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18509647 M.J.Stasia, and X.J.Li (2008).
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PDB code: 2rmk
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18347018 Y.Y.Kao, D.Gianni, B.Bohl, R.M.Taylor, and G.M.Bokoch (2008).
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Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes.
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PDB codes: 2ond 2ooe
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16987009 G.M.Bokoch, and T.Zhao (2006).
Regulation of the phagocyte NADPH oxidase by Rac GTPase.
  Antioxid Redox Signal, 8, 1533-1548.  
16762923 K.Miyano, N.Ueno, R.Takeya, and H.Sumimoto (2006).
Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1.
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16987008 R.Takeya, and H.Sumimoto (2006).
Regulation of novel superoxide-producing NAD(P)H oxidases.
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Rac GTPase signaling through the PP5 protein phosphatase.
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The crystal structure of NlpI. A prokaryotic tetratricopeptide repeat protein with a globular fold.
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PDB code: 1xnf
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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, 280, 13752-13761.
PDB codes: 1w6x 1w70
15752980 G.M.Bokoch (2005).
Regulation of innate immunity by Rho GTPases.
  Trends Cell Biol, 15, 163-171.  
15935782 J.Kim, S.Sitaraman, A.Hierro, B.M.Beach, G.Odorizzi, and J.H.Hurley (2005).
Structural basis for endosomal targeting by the Bro1 domain.
  Dev Cell, 8, 937-947.
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  Mol Cell, 20, 313-324.
PDB code: 2atx
15824103 N.Ueno, R.Takeya, K.Miyano, H.Kikuchi, and H.Sumimoto (2005).
The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators.
  J Biol Chem, 280, 23328-23339.  
14999155 A.E.Karnoub, M.Symons, S.L.Campbell, and C.J.Der (2004).
Molecular basis for Rho GTPase signaling specificity.
  Breast Cancer Res Treat, 84, 61-71.  
15123662 B.A.Diebold, B.Fowler, J.Lu, M.C.Dinauer, and G.M.Bokoch (2004).
Antagonistic cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species.
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14625275 D.Fiegen, L.C.Haeusler, L.Blumenstein, U.Herbrand, R.Dvorsky, I.R.Vetter, and M.R.Ahmadian (2004).
Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.
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PDB codes: 1ryf 1ryh
14705031 J.A.Dohm, S.J.Lee, J.M.Hardwick, R.B.Hill, and A.G.Gittis (2004).
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  Proteins, 54, 153-156.
PDB code: 1nzn
15039755 J.D.Lambeth (2004).
NOX enzymes and the biology of reactive oxygen.
  Nat Rev Immunol, 4, 181-189.  
15365846 J.M.Robinson, T.Ohira, and J.A.Badwey (2004).
Regulation of the NADPH-oxidase complex of phagocytic leukocytes. Recent insights from structural biology, molecular genetics, and microscopy.
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The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha.
  Nat Struct Mol Biol, 11, 1001-1007.
PDB code: 1w3b
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Hop: more than an Hsp70/Hsp90 adaptor protein.
  Bioessays, 26, 1058-1068.  
14660612 R.Dvorsky, L.Blumenstein, I.R.Vetter, and M.R.Ahmadian (2004).
Structural insights into the interaction of ROCKI with the switch regions of RhoA.
  J Biol Chem, 279, 7098-7104.
PDB code: 1s1c
15577926 R.Dvorsky, and M.R.Ahmadian (2004).
Always look on the bright site of Rho: structural implications for a conserved intermolecular interface.
  EMBO Rep, 5, 1130-1136.  
14761978 R.Sarfstein, Y.Gorzalczany, A.Mizrahi, Y.Berdichevsky, S.Molshanski-Mor, C.Weinbaum, M.Hirshberg, M.C.Dagher, and E.Pick (2004).
Dual role of Rac in the assembly of NADPH oxidase, tethering to the membrane and activation of p67phox: a study based on mutagenesis of p67phox-Rac1 chimeras.
  J Biol Chem, 279, 16007-16016.  
15102859 S.Hashida, S.Yuzawa, N.N.Suzuki, Y.Fujioka, T.Takikawa, H.Sumimoto, F.Inagaki, and H.Fujii (2004).
Binding of FAD to cytochrome b558 is facilitated during activation of the phagocyte NADPH oxidase, leading to superoxide production.
  J Biol Chem, 279, 26378-26386.  
12473664 B.Bánfi, R.A.Clark, K.Steger, and K.H.Krause (2003).
Two novel proteins activate superoxide generation by the NADPH oxidase NOX1.
  J Biol Chem, 278, 3510-3513.  
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Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1).
  J Biol Chem, 278, 50578-50587.
PDB code: 1urf
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Design of stable alpha-helical arrays from an idealized TPR motif.
  Structure, 11, 497-508.
PDB codes: 1na0 1na3
13678962 G.M.Bokoch, and U.G.Knaus (2003).
NADPH oxidases: not just for leukocytes anymore!
  Trends Biochem Sci, 28, 502-508.  
12483106 M.C.Dinauer (2003).
Regulation of neutrophil function by Rac GTPases.
  Curr Opin Hematol, 10, 8.  
12657628 M.Geiszt, K.Lekstrom, J.Witta, and T.L.Leto (2003).
Proteins homologous to p47phox and p67phox support superoxide production by NAD(P)H oxidase 1 in colon epithelial cells.
  J Biol Chem, 278, 20006-20012.  
12887891 M.I.Wilson, D.J.Gill, O.Perisic, M.T.Quinn, and R.L.Williams (2003).
PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62.
  Mol Cell, 12, 39-50.
PDB code: 1oey
12799000 M.J.Pallen, M.S.Francis, and K.Fütterer (2003).
Tetratricopeptide-like repeats in type-III-secretion chaperones and regulators.
  FEMS Microbiol Lett, 223, 53-60.
PDB codes: 1ool 1oom 1ooo 1oor 1oos
12475976 N.Sigal, Y.Gorzalczany, R.Sarfstein, C.Weinbaum, Y.Zheng, and E.Pick (2003).
The guanine nucleotide exchange factor trio activates the phagocyte NADPH oxidase in the absence of GDP to GTP exchange on Rac. "The emperor's nw clothes".
  J Biol Chem, 278, 4854-4861.  
14506233 P.Matos, J.G.Collard, and P.Jordan (2003).
Tumor-related alternatively spliced Rac1b is not regulated by Rho-GDP dissociation inhibitors and exhibits selective downstream signaling.
  J Biol Chem, 278, 50442-50448.  
12594026 R.Kong, X.Xu, and Z.Hu (2003).
A TPR-family membrane protein gene is required for light-activated heterotrophic growth of the cyanobacterium Synechocystis sp. PCC 6803.
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12716910 R.Takeya, N.Ueno, K.Kami, M.Taura, M.Kohjima, T.Izaki, H.Nunoi, and H.Sumimoto (2003).
Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases.
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The molecular basis for adhesion-mediated suppression of reactive oxygen species generation by human neutrophils.
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12912997 X.Zhao, K.A.Carnevale, and M.K.Cathcart (2003).
Human monocytes use Rac1, not Rac2, in the NADPH oxidase complex.
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12930823 Y.Liao, I.M.Willis, and R.D.Moir (2003).
The Brf1 and Bdp1 subunits of transcription factor TFIIIB bind to overlapping sites in the tetratricopeptide repeats of Tfc4.
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Ligand discrimination by TPR domains. Relevance and selectivity of EEVD-recognition in Hsp70 x Hop x Hsp90 complexes.
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11733522 I.Dahan, I.Issaeva, Y.Gorzalczany, N.Sigal, M.Hirshberg, and E.Pick (2002).
Mapping of functional domains in the p22(phox) subunit of flavocytochrome b(559) participating in the assembly of the NADPH oxidase complex by "peptide walking".
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Rac activation induces NADPH oxidase activity in transgenic COSphox cells, and the level of superoxide production is exchange factor-dependent.
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Domain structure of the HSC70 cochaperone, HIP.
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12186557 P.Moskwa, M.C.Dagher, M.H.Paclet, F.Morel, and E.Ligeti (2002).
Participation of Rac GTPase activating proteins in the deactivation of the phagocytic NADPH oxidase.
  Biochemistry, 41, 10710-10716.  
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Autoinhibition of TFIIIB70 binding by the tetratricopeptide repeat-containing subunit of TFIIIC.
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12011045 S.J.Walker, and H.A.Brown (2002).
Specificity of Rho insert-mediated activation of phospholipase D1.
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Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae.
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A prenylated p67phox-Rac1 chimera elicits NADPH-dependent superoxide production by phagocyte membranes in the absence of an activator and of p47phox: conversion of a pagan NADPH oxidase to monotheism.
  J Biol Chem, 277, 18605-18610.  
11709169 C.Steegborn, O.Danot, R.Huber, and T.Clausen (2001).
Crystal structure of transcription factor MalT domain III: a novel helix repeat fold implicated in regulated oligomerization.
  Structure, 9, 1051-1060.
PDB code: 1hz4
11701921 I.R.Vetter, and A.Wittinghofer (2001).
The guanine nucleotide-binding switch in three dimensions.
  Science, 294, 1299-1304.  
11738594 K.D.Corbett, and T.Alber (2001).
The many faces of Ras: recognition of small GTP-binding proteins.
  Trends Biochem Sci, 26, 710-716.  
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Kinesin carries the signal.
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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.