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PDBsum entry 1ucf

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protein Protein-protein interface(s) links
RNA binding protein PDB id
1ucf
Jmol
Contents
Protein chain
188 a.a. *
Waters ×321
* Residue conservation analysis
PDB id:
1ucf
Name: RNA binding protein
Title: The crystal structure of dj-1, a protein related to male fertility and parkinson's disease
Structure: RNA-binding protein regulatory subunit. Chain: a, b. Synonym: dj-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: dj-1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
Resolution:
1.95Å     R-factor:   0.170     R-free:   0.195
Authors: K.Honbou,N.N.Suzuki,M.Horiuchi,T.Niki,T.Taira,H.Ariga, F.Inagaki
Key ref:
K.Honbou et al. (2003). The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease. J Biol Chem, 278, 31380-31384. PubMed id: 12796482 DOI: 10.1074/jbc.M305878200
Date:
11-Apr-03     Release date:   19-Aug-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q99497  (PARK7_HUMAN) -  Protein DJ-1
Seq:
Struc:
189 a.a.
188 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   11 terms 
  Biological process     response to stress   65 terms 
  Biochemical function     protein binding     31 terms  

 

 
DOI no: 10.1074/jbc.M305878200 J Biol Chem 278:31380-31384 (2003)
PubMed id: 12796482  
 
 
The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease.
K.Honbou, N.N.Suzuki, M.Horiuchi, T.Niki, T.Taira, H.Ariga, F.Inagaki.
 
  ABSTRACT  
 
DJ-1 is a multifunctional protein that plays essential roles in tissues with higher order biological functions such as the testis and brain. DJ-1 is related to male fertility, and its level in sperm decreases in response to exposure to sperm toxicants. DJ-1 has also been identified as a hydroperoxide-responsive protein. Recently, a mutation of DJ-1 was found to be responsible for familial Parkinson's disease. Here, we present the crystal structure of DJ-1 refined to 1.95-A resolution. DJ-1 forms a dimer in the crystal, and the monomer takes a flavodoxin-like Rossmann-fold. DJ-1 is structurally most similar to the monomer subunit of protease I, the intracellular cysteine protease from Pyrococcus horikoshii, and belongs to the Class I glutamine amidotransferase-like superfamily. However, DJ-1 contains an additional alpha-helix at the C-terminal region, which blocks the putative catalytic site of DJ-1 and appears to regulate the enzymatic activity. DJ-1 may induce conformational changes to acquire catalytic activity in response to oxidative stress.
 
  Selected figure(s)  
 
Figure 3.
FIG. 3. Surface representations of the dimer interface and the opposite surface of DJ-1. The electrostatic surface potential of DJ-1 for the dimer interface (a) and the opposite surface (b) is shown. Red and blue represent negative and positive potentials, respectively. The surface model for the dimer interface (c) and the opposite surface of DJ-1 (d) in which the binding surface is encircled with a solid line are shown. The conserved and type conserved residues are shown in red and yellow, respectively. Compared with the opposite surface, the residues on the dimer interface are either conserved or type-conserved. Notably, the residues forming the putative catalytic site (encircled with a dotted line) are located close to the dimer interface and are highly conserved. Fig. 3 was prepared using GRASP (29).
Figure 4.
FIG. 4. Comparison of the monomer structures and the putative catalytic sites between DJ-1 and protease I. Ribbon diagrams of the monomer subunits of DJ-1 (a) and protease I (b). Secondary structure is color-coded as in Fig. 2a. c, the region around the putative active site of DJ-1 including 5, 5, and the nucleophile elbow in monomer A (in blue) and 8 and 9 in monomer B (in green). The residues Cys-106, His-126, and Val-128 in monomer A and Leu-166, Val-181, Lys-182, Pro-184 (a backbone oxygen), Val-186, and Leu-187 in monomer B are shown as ball-and-stick models. The His-126 imidazole ring forms hydrogen bonds with the main-chain carbonyl group of Pro-184 (monomer B) and the main-chain amide group of Val-128 (monomer A) are shown by the dotted lines. Thus, the His-126 imidazole ring does not take a preferable orientation for protease activity. Leu-166, mutated to proline in PARK7 patients, is shown in red. d, the region around the active site of protease I including the nucleophile elbow in which the catalytic residue Cys-100 is located. Protease I forms a hexamer, and the catalytic triad is formed in the dimer interface (monomer A is in blue, and monomer B is in green).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 31380-31384) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308111 M.Eltoweissy, G.A.Müller, A.Bibi, P.V.Nguye, G.H.Dihazi, C.A.Müller, and H.Dihazi (2011).
Proteomics analysis identifies PARK7 as an important player for renal cell resistance and survival under oxidative stress.
  Mol Biosyst, 7, 1277-1288.  
20304780 J.Chen, L.Li, and L.S.Chin (2010).
Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage.
  Hum Mol Genet, 19, 2395-2408.  
20156966 S.Deeg, M.Gralle, K.Sroka, M.Bähr, F.S.Wouters, and P.Kermer (2010).
BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity.
  J Cell Biol, 188, 505-513.  
20014998 U.Saeed, A.Ray, R.K.Valli, A.M.Kumar, and V.Ravindranath (2010).
DJ-1 loss by glutaredoxin but not glutathione depletion triggers Daxx translocation and cell death.
  Antioxid Redox Signal, 13, 127-144.  
18711745 E.Junn, W.H.Jang, X.Zhao, B.S.Jeong, and M.M.Mouradian (2009).
Mitochondrial localization of DJ-1 leads to enhanced neuroprotection.
  J Neurosci Res, 87, 123-129.  
19293155 J.Waak, S.S.Weber, K.Görner, C.Schall, H.Ichijo, T.Stehle, and P.J.Kahle (2009).
Oxidizable residues mediating protein stability and cytoprotective interaction of DJ-1 with apoptosis signal-regulating kinase 1.
  J Biol Chem, 284, 14245-14257.  
20087465 K.Yamane, Y.Kitamura, T.Yanagida, K.Takata, D.Yanagisawa, T.Taniguchi, T.Taira, and H.Ariga (2009).
Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson's Disease-Linked PARK7.
  Int J Mol Sci, 10, 4789-4804.  
19686841 P.J.Kahle, J.Waak, and T.Gasser (2009).
DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders.
  Free Radic Biol Med, 47, 1354-1361.  
  20046643 T.Yanagida, J.Tsushima, Y.Kitamura, D.Yanagisawa, K.Takata, T.Shibaike, A.Yamamoto, T.Taniguchi, H.Yasui, T.Taira, S.Morikawa, T.Inubushi, I.Tooyama, and H.Ariga (2009).
Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
  Oxid Med Cell Longev, 2, 36-42.  
18570440 A.C.Witt, M.Lakshminarasimhan, B.C.Remington, S.Hasim, E.Pozharski, and M.A.Wilson (2008).
Cysteine pKa depression by a protonated glutamic acid in human DJ-1.
  Biochemistry, 47, 7430-7440.
PDB codes: 2or3 3cy6 3cyf 3cz9 3cza
17882163 D.Yanagisawa, Y.Kitamura, M.Inden, K.Takata, T.Taniguchi, S.Morikawa, M.Morita, T.Inubushi, I.Tooyama, T.Taira, S.M.Iguchi-Ariga, A.Akaike, and H.Ariga (2008).
DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats.
  J Cereb Blood Flow Metab, 28, 563-578.  
18313759 F.J.Lee, and F.Liu (2008).
Genetic factors involved in the pathogenesis of Parkinson's disease.
  Brain Res Rev, 58, 354-364.  
18436956 G.Malgieri, and D.Eliezer (2008).
Structural effects of Parkinson's disease linked DJ-1 mutations.
  Protein Sci, 17, 855-868.  
18505826 G.S.Butler, R.A.Dean, E.M.Tam, and C.M.Overall (2008).
Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding.
  Mol Cell Biol, 28, 4896-4914.  
18309325 J.S.Mo, M.Y.Kim, E.J.Ann, J.A.Hong, and H.S.Park (2008).
DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death.
  Cell Death Differ, 15, 1030-1041.  
18181649 M.Lakshminarasimhan, M.T.Maldonado, W.Zhou, A.L.Fink, and M.A.Wilson (2008).
Structural impact of three Parkinsonism-associated missense mutations on human DJ-1.
  Biochemistry, 47, 1381-1392.
PDB codes: 2rk3 2rk4 2rk6 3b36 3b38 3b3a
18707128 P.C.Anderson, and V.Daggett (2008).
Molecular basis for the structural instability of human DJ-1 induced by the L166P mutation associated with Parkinson's disease.
  Biochemistry, 47, 9380-9393.  
18922803 S.S.Cha, H.I.Jung, H.Jeon, Y.J.An, I.K.Kim, S.Yun, H.J.Ahn, K.C.Chung, S.H.Lee, P.G.Suh, and S.O.Kang (2008).
Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner.
  J Biol Chem, 283, 34069-34075.
PDB code: 3bwe
17766438 E.Andres-Mateos, C.Perier, L.Zhang, B.Blanchard-Fillion, T.M.Greco, B.Thomas, H.S.Ko, M.Sasaki, H.Ischiropoulos, S.Przedborski, T.M.Dawson, and V.L.Dawson (2007).
DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase.
  Proc Natl Acad Sci U S A, 104, 14807-14812.  
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.  
16390825 A.Sekito, S.Koide-Yoshida, T.Niki, T.Taira, S.M.Iguchi-Ariga, and H.Ariga (2006).
DJ-1 interacts with HIPK1 and affects H2O2-induced cell death.
  Free Radic Res, 40, 155-165.  
16819732 J.Martínez-Heredia, J.M.Estanyol, J.L.Ballescà, and R.Oliva (2006).
Proteomic identification of human sperm proteins.
  Proteomics, 6, 4356-4369.  
16894167 M.C.Meulener, K.Xu, L.Thomson, L.Thompson, H.Ischiropoulos, and N.M.Bonini (2006).
Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.
  Proc Natl Acad Sci U S A, 103, 12517-12522.  
16495942 P.M.Abou-Sleiman, M.M.Muqit, and N.W.Wood (2006).
Expanding insights of mitochondrial dysfunction in Parkinson's disease.
  Nat Rev Neurosci, 7, 207-219.  
16615060 S.Kubo, N.Hattori, and Y.Mizuno (2006).
Recessive Parkinson's disease.
  Mov Disord, 21, 885-893.  
16823625 T.Nagatsu, and M.Sawada (2006).
Cellular and molecular mechanisms of Parkinson's disease: neurotoxins, causative genes, and inflammatory cytokines.
  Cell Mol Neurobiol, 26, 781-802.  
15976810 Y.Shinbo, T.Niki, T.Taira, H.Ooe, K.Takahashi-Niki, C.Maita, C.Seino, S.M.Iguchi-Ariga, and H.Ariga (2006).
Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities.
  Cell Death Differ, 13, 96.  
16298734 H.M.Li, T.Niki, T.Taira, S.M.Iguchi-Ariga, and H.Ariga (2005).
Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress.
  Free Radic Res, 39, 1091-1099.  
15935068 M.C.Meulener, C.L.Graves, D.M.Sampathu, C.E.Armstrong-Gold, N.M.Bonini, and B.I.Giasson (2005).
DJ-1 is present in a large molecular complex in human brain tissue and interacts with alpha-synuclein.
  J Neurochem, 93, 1524-1532.  
15766664 R.H.Kim, M.Peters, Y.Jang, W.Shi, M.Pintilie, G.C.Fletcher, C.DeLuca, J.Liepa, L.Zhou, B.Snow, R.C.Binari, A.S.Manoukian, M.R.Bray, F.F.Liu, M.S.Tsao, and T.W.Mak (2005).
DJ-1, a novel regulator of the tumor suppressor PTEN.
  Cancer Cell, 7, 263-273.  
15112332 A.B.Siva, V.R.Sundareswaran, C.H.Yeung, T.G.Cooper, and S.Shivaji (2004).
Hamster contraception associated protein 1 (CAP1).
  Mol Reprod Dev, 68, 373-383.  
15272266 E.Bossy-Wetzel, R.Schwarzenbacher, and S.A.Lipton (2004).
Molecular pathways to neurodegeneration.
  Nat Med, 10, S2-S9.  
14745011 M.A.Wilson, C.V.St Amour, J.L.Collins, D.Ringe, and G.A.Petsko (2004).
The 1.8-A resolution crystal structure of YDR533Cp from Saccharomyces cerevisiae: a member of the DJ-1/ThiJ/PfpI superfamily.
  Proc Natl Acad Sci U S A, 101, 1531-1536.
PDB code: 1rw7
15130476 M.Graille, S.Quevillon-Cheruel, N.Leulliot, C.Z.Zhou, I.Li de la Sierra Gallay, L.Jacquamet, J.L.Ferrer, D.Liger, A.Poupon, J.Janin, and H.van Tilbeurgh (2004).
Crystal structure of the YDR533c S. cerevisiae protein, a class II member of the Hsp31 family.
  Structure, 12, 839-847.
PDB codes: 1qvv 1qvw 1qvz
15173574 M.S.Sastry, P.M.Quigley, W.G.Hol, and F.Baneyx (2004).
The linker-loop region of Escherichia coli chaperone Hsp31 functions as a gate that modulates high-affinity substrate binding at elevated temperatures.
  Proc Natl Acad Sci U S A, 101, 8587-8592.  
15503154 P.M.Abou-Sleiman, D.G.Healy, and N.W.Wood (2004).
Causes of Parkinson's disease: genetics of DJ-1.
  Cell Tissue Res, 318, 185-188.  
15181200 R.M.Canet-Avilés, M.A.Wilson, D.W.Miller, R.Ahmad, C.McLendon, S.Bandyopadhyay, M.J.Baptista, D.Ringe, G.A.Petsko, and M.R.Cookson (2004).
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.
  Proc Natl Acad Sci U S A, 101, 9103-9108.
PDB code: 1soa
15070401 S.Bandyopadhyay, and M.R.Cookson (2004).
Evolutionary and functional relationships within the DJ1 superfamily.
  BMC Evol Biol, 4, 6.  
15502874 S.Shendelman, A.Jonason, C.Martinat, T.Leete, and A.Abeliovich (2004).
DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation.
  PLoS Biol, 2, e362.  
14749723 T.Taira, Y.Saito, T.Niki, S.M.Iguchi-Ariga, K.Takahashi, and H.Ariga (2004).
DJ-1 has a role in antioxidative stress to prevent cell death.
  EMBO Rep, 5, 213-218.  
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 codes are shown on the right.