PDBsum entry 1oey

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protein Protein-protein interface(s) links
Immune system PDB id
Protein chains
82 a.a. *
77 a.a. *
105 a.a. *
99 a.a. *
Waters ×343
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Heterodimer of p40phox and p67phox pb1 domains from human NADPH oxidase
Structure: Neutrophil cytosol factor 2. Chain: a, b, c, d. Fragment: pb1 domain, residues 352-429. Synonym: p67-phox. Engineered: yes. Neutrophil cytosol factor 4. Chain: j, k, l, m. Fragment: pb1 domain, residues 237-339. Synonym: p40-phox.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
2.00Å     R-factor:   0.212     R-free:   0.252
Authors: M.I.Wilson,D.J.Gill,O.Perisic,M.T.Quinn,R.L.Williams
Key ref:
M.I.Wilson et al. (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. PubMed id: 12887891 DOI: 10.1016/S1097-2765(03)00246-6
02-Apr-03     Release date:   29-Jul-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P19878  (NCF2_HUMAN) -  Neutrophil cytosol factor 2
526 a.a.
82 a.a.*
Protein chains
Pfam   ArchSchema ?
P19878  (NCF2_HUMAN) -  Neutrophil cytosol factor 2
526 a.a.
77 a.a.*
Protein chains
Pfam   ArchSchema ?
Q15080  (NCF4_HUMAN) -  Neutrophil cytosol factor 4
339 a.a.
105 a.a.*
Protein chains
Pfam   ArchSchema ?
Q15080  (NCF4_HUMAN) -  Neutrophil cytosol factor 4
339 a.a.
99 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)


DOI no: 10.1016/S1097-2765(03)00246-6 Mol Cell 12:39-50 (2003)
PubMed id: 12887891  
PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62.
M.I.Wilson, D.J.Gill, O.Perisic, M.T.Quinn, R.L.Williams.
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.
  Selected figure(s)  
Figure 3.
Figure 3. Surface Representations of the p40^phox PB1/p67^phox PB1 Heterodimer Showing the Distinct Electrostatic Complementarity of the Interface(A) The “front” surface of p40^phox PB1. The negative AC1 and AC2 patches on the “front” surface of p40^phox PB1 interact with the positive BC1 and BC2, respectively, on the “back” of p67^phox PB1. The surface of p40^phox PB1 is colored by electrostatic potential (blue positive and red negative), and the p67^phox PB1 is shown as a cyan-colored worm.(B) The “back” surface of p67^phox PB1 colored by electrostatic potential as in (A). The p40^phox PB1 is shown as a yellow-colored worm.(C) The p40^phox PB1 has a concave “front” face into which the convex “back” face of p67^phox PB1 fits. The representation is as in (A) with a view of the heterodimer rotated approximately 90° around the horizontal and vertical axes.(D) The charged residues in the acidic and basic clusters at the p40^phox PB1/p67^phox PB1 interface are shown as balls and sticks. The view is rotated 180° about the horizontal axis relative to the view shown in (C).
Figure 4.
Figure 4. Details of the Interactions at the p40^phox PB1/p67^phox PB1 Heterodimer InterfaceThe domains are colored as in Figure 1. Dashed lines represent intermolecular hydrogen bonds. The side chains of residues involved in intermolecular hydrogen bonds or complementary electrostatic interactions as described in the text are shown as sticks.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 12, 39-50) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21220506 E.Itakura, and N.Mizushima (2011).
p62 targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.
  J Cell Biol, 192, 17-27.  
20945390 N.R.Murray, K.R.Kalari, and A.P.Fields (2011).
Protein kinase Cι expression and oncogenic signaling mechanisms in cancer.
  J Cell Physiol, 226, 879-887.  
20122916 J.Li, H.Kim, D.G.Aceto, J.Hung, S.Aono, and K.J.Kemphues (2010).
Binding to PKC-3, but not to PAR-3 or to a conventional PDZ domain ligand, is required for PAR-6 function in C. elegans.
  Dev Biol, 340, 88-98.  
19903815 K.Nakamura, A.J.Kimple, D.P.Siderovski, and G.L.Johnson (2010).
PB1 domain interaction of p62/sequestosome 1 and MEKK3 regulates NF-kappaB activation.
  J Biol Chem, 285, 2077-2089.  
20105302 K.Robison (2010).
Re-examination of chimp protein kinases suggests "novel architectures" are gene prediction artifacts.
  BMC Genomics, 11, 66.  
20018885 S.Pankiv, T.Lamark, J.A.Bruun, A.Øvervatn, G.Bjørkøy, and T.Johansen (2010).
Nucleocytoplasmic shuttling of p62/SQSTM1 and its role in recruitment of nuclear polyubiquitinated proteins to promyelocytic leukemia bodies.
  J Biol Chem, 285, 5941-5953.  
20300805 T.Saio, M.Yokochi, H.Kumeta, and F.Inagaki (2010).
PCS-based structure determination of protein-protein complexes.
  J Biomol NMR, 46, 271-280.
PDB code: 2ktr
19765191 J.Gal, A.L.Ström, D.M.Kwinter, R.Kilty, J.Zhang, P.Shi, W.Fu, M.W.Wooten, and H.Zhu (2009).
Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism.
  J Neurochem, 111, 1062-1073.  
19451149 K.Ogura, T.Tandai, S.Yoshinaga, Y.Kobashigawa, H.Kumeta, T.Ito, H.Sumimoto, and F.Inagaki (2009).
NMR structure of the heterodimer of Bem1 and Cdc24 PB1 domains from Saccharomyces cerevisiae.
  J Biochem, 146, 317-325.
PDB codes: 2kfj 2kfk
19728111 T.Saio, M.Yokochi, and F.Inagaki (2009).
The NMR structure of the p62 PB1 domain, a key protein in autophagy and NF-kappaB signaling pathway.
  J Biomol NMR, 45, 335-341.
PDB code: 2kkc
18513324 H.Sumimoto (2008).
Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species.
  FEBS J, 275, 3249-3277.  
18922891 M.E.Nolan, V.Aranda, S.Lee, B.Lakshmi, S.Basu, D.C.Allred, and S.K.Muthuswamy (2008).
The polarity protein Par6 induces cell proliferation and is overexpressed in breast cancer.
  Cancer Res, 68, 8201-8209.  
17296612 J.Gal, A.L.Ström, R.Kilty, F.Zhang, and H.Zhu (2007).
p62 accumulates and enhances aggregate formation in model systems of familial amyotrophic lateral sclerosis.
  J Biol Chem, 282, 11068-11077.  
17290225 K.Honbou, R.Minakami, S.Yuzawa, R.Takeya, N.N.Suzuki, S.Kamakura, H.Sumimoto, and F.Inagaki (2007).
Full-length p40phox structure suggests a basis for regulation mechanism of its membrane binding.
  EMBO J, 26, 1176-1186.
PDB code: 2dyb
17452462 K.Nakamura, and G.L.Johnson (2007).
Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase signaling.
  Mol Cell Biol, 27, 4566-4577.  
17188686 M.L.Seibenhener, T.Geetha, and M.W.Wooten (2007).
Sequestosome 1/p62--more than just a scaffold.
  FEBS Lett, 581, 175-179.  
17580304 S.Pankiv, T.H.Clausen, T.Lamark, A.Brech, J.A.Bruun, H.Outzen, A.Øvervatn, G.Bjørkøy, and T.Johansen (2007).
p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.
  J Biol Chem, 282, 24131-24145.  
17900370 T.Kawahara, and J.D.Lambeth (2007).
Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes.
  BMC Evol Biol, 7, 178.  
17122360 T.Ueyama, T.Tatsuno, T.Kawasaki, S.Tsujibe, Y.Shirai, H.Sumimoto, T.L.Leto, and N.Saito (2007).
A regulated adaptor function of p40phox: distinct p67phox membrane targeting by p40phox and by p47phox.
  Mol Biol Cell, 18, 441-454.  
17476308 W.Feng, H.Wu, L.N.Chan, and M.Zhang (2007).
The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization.
  EMBO J, 26, 2786-2796.
PDB code: 2ns5
16880254 C.D.Ellson, K.Davidson, G.J.Ferguson, R.O'Connor, L.R.Stephens, and P.T.Hawkins (2006).
Neutrophils from p40phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing.
  J Exp Med, 203, 1927-1937.  
16880255 C.I.Suh, N.D.Stull, X.J.Li, W.Tian, M.O.Price, S.Grinstein, M.B.Yaffe, S.Atkinson, and M.C.Dinauer (2006).
The phosphoinositide-binding protein p40phox activates the NADPH oxidase during FcgammaIIA receptor-induced phagocytosis.
  J Exp Med, 203, 1915-1925.  
16861740 E.Erdogan, T.Lamark, M.Stallings-Mann, Lee Jamieson, M.Pellecchia, M.Pellechia, E.A.Thompson, T.Johansen, and A.P.Fields (2006).
Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase Ciota.
  J Biol Chem, 281, 28450-28459.  
16949360 J.Moscat, M.T.Diaz-Meco, A.Albert, and S.Campuzano (2006).
Cell signaling and function organized by PB1 domain interactions.
  Mol Cell, 23, 631-640.  
16322752 J.Moscat, P.Rennert, and M.T.Diaz-Meco (2006).
PKCzeta at the crossroad of NF-kappaB and Jak1/Stat6 signaling pathways.
  Cell Death Differ, 13, 702-711.  
  17012801 K.Honbou, S.Yuzawa, N.N.Suzuki, Y.Fujioka, H.Sumimoto, and F.Inagaki (2006).
Crystallization and preliminary crystallographic analysis of p40phox, a regulatory subunit of NADPH oxidase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1018-1020.  
16507987 K.Nakamura, M.T.Uhlik, N.L.Johnson, K.M.Hahn, and G.L.Johnson (2006).
PB1 domain-dependent signaling complex is required for extracellular signal-regulated kinase 5 activation.
  Mol Cell Biol, 26, 2065-2079.  
17060907 V.Aranda, T.Haire, M.E.Nolan, J.P.Calarco, A.Z.Rosenberg, J.P.Fawcett, T.Pawson, and S.K.Muthuswamy (2006).
Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control.
  Nat Cell Biol, 8, 1235-1245.  
15657040 C.Massenet, S.Chenavas, C.Cohen-Addad, M.C.Dagher, G.Brandolin, E.Pebay-Peyroula, and F.Fieschi (2005).
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
15798205 J.H.Kim, J.H.Kim, M.Ohba, P.G.Suh, and S.H.Ryu (2005).
Novel functions of the phospholipase D2-Phox homology domain in protein kinase Czeta activation.
  Mol Cell Biol, 25, 3194-3208.  
15712318 M.Jenny, O.A.Wrulich, W.Schwaiger, and F.Ueberall (2005).
Relevance of atypical protein kinase C isotypes to the drug discovery process.
  Chembiochem, 6, 491-499.  
15772751 M.Schubert, D.Labudde, D.Leitner, H.Oschkinat, and P.Schmieder (2005).
A modified strategy for sequence specific assignment of protein NMR spectra based on amino acid type selective experiments.
  J Biomol NMR, 31, 115-128.  
15590654 Y.Hirano, S.Yoshinaga, R.Takeya, N.N.Suzuki, M.Horiuchi, M.Kohjima, H.Sumimoto, and F.Inagaki (2005).
Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains.
  J Biol Chem, 280, 9653-9661.
PDB code: 1wmh
15364906 B.L.Lytle, F.C.Peterson, S.H.Qiu, M.Luo, Q.Zhao, J.L.Markley, and B.F.Volkman (2004).
Solution structure of a ubiquitin-like domain from tubulin-binding cofactor B.
  J Biol Chem, 279, 46787-46793.
PDB code: 1t0y
15365659 R.Layfield, and L.J.Hocking (2004).
SQSTM1 and Paget's disease of bone.
  Calcif Tissue Int, 75, 347-357.  
15143057 Y.Hirano, S.Yoshinaga, K.Ogura, M.Yokochi, Y.Noda, H.Sumimoto, and F.Inagaki (2004).
Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5.
  J Biol Chem, 279, 31883-31890.
PDB code: 1vd2
12912994 K.Nakamura, and G.L.Johnson (2003).
PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway.
  J Biol Chem, 278, 36989-36992.  
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.