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PDBsum entry 2b5l

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protein metals Protein-protein interface(s) links
Protein binding/viral protein PDB id
2b5l

 

 

 

 

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Contents
Protein chains
1132 a.a. *
174 a.a. *
Metals
_ZN ×4
* Residue conservation analysis
PDB id:
2b5l
Name: Protein binding/viral protein
Title: Crystal structure of ddb1 in complex with simian virus 5 v protein
Structure: Damage-specific DNA binding protein 1. Chain: a, b. Engineered: yes. Nonstructural protein v. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Simian virus 5. Organism_taxid: 11207. Gene: p/v. Expressed in: escherichia coli.
Biol. unit: Dimer (from PQS)
Resolution:
2.85Å     R-factor:   0.229     R-free:   0.299
Authors: T.Li,X.Chen,K.C.Garbutt,P.Zhou,N.Zheng
Key ref:
T.Li et al. (2006). Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell, 124, 105-117. PubMed id: 16413485 DOI: 10.1016/j.cell.2005.10.033
Date:
28-Sep-05     Release date:   28-Feb-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q16531  (DDB1_HUMAN) -  DNA damage-binding protein 1 from Homo sapiens
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1140 a.a.
1132 a.a.*
Protein chains
Pfam   ArchSchema ?
P11207  (V_PIV5) -  Non-structural protein V from Parainfluenza virus 5 (strain W3)
Seq:
Struc:
222 a.a.
174 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 

 
DOI no: 10.1016/j.cell.2005.10.033 Cell 124:105-117 (2006)
PubMed id: 16413485  
 
 
Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.
T.Li, X.Chen, K.C.Garbutt, P.Zhou, N.Zheng.
 
  ABSTRACT  
 
The DDB1-Cul4A ubiquitin ligase complex promotes protein ubiquitination in diverse cellular functions and is reprogrammed by the V proteins of paramyxoviruses to degrade STATs and block interferon signaling. Here we report the crystal structures of DDB1 alone and in complex with the simian virus 5 V protein. The DDB1 structure reveals an intertwined three-propeller cluster, which contains two tightly coupled beta propellers with a large pocket in between and a third beta propeller flexibly attached on the side. The rigid double-propeller fold of DDB1 is targeted by the viral V protein, which inserts an entire helix into the double-propeller pocket, whereas the third propeller domain docks DDB1 to the N terminus of the Cul4A scaffold. Together, these results not only provide structural insights into how the virus hijacks the DDB1-Cul4A ubiquitin ligase but also establish a structural framework for understanding the multiple functions of DDB1 in the uniquely assembled cullin-RING E3 machinery.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Multiple Potential Protein Interaction Sites Are Found in the Double-Propeller Fold Formed by BPA and BPC of DDB1
Figure 4.
Figure 4. Interactions between DDB1 and Cul4A Involve the Top Surface of the DDB1 BPB Domain and a Conserved Sequence Motif of Cul4A N-Terminal to the First Cullin Repeat
 
  The above figures are reprinted by permission from Cell Press: Cell (2006, 124, 105-117) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22158412 X.Jiang, and Z.J.Chen (2012).
The role of ubiquitylation in immune defence and pathogen evasion.
  Nat Rev Immunol, 12, 35-48.  
21554755 A.Sarikas, T.Hartmann, and Z.Q.Pan (2011).
The cullin protein family.
  Genome Biol, 12, 220.  
21468892 C.Xu, and J.Min (2011).
Structure and function of WD40 domain proteins.
  Protein Cell, 2, 202-214.
PDB codes: 3e0c 3fm0 3i2n 3ow8
20499085 A.Bernhardt, S.Mooney, and H.Hellmann (2010).
Arabidopsis DDB1a and DDB1b are critical for embryo development.
  Planta, 232, 555-566.  
20427537 A.Röthlisberger, D.Wiener, M.Schweizer, E.Peterhans, A.Zurbriggen, and P.Plattet (2010).
Two domains of the V protein of virulent canine distemper virus selectively inhibit STAT1 and STAT2 nuclear import.
  J Virol, 84, 6328-6343.  
20451393 C.U.Stirnimann, E.Petsalaki, R.B.Russell, and C.W.Müller (2010).
WD40 proteins propel cellular networks.
  Trends Biochem Sci, 35, 565-574.  
19906928 D.Qiao, B.H.Janke, and S.Elankumaran (2010).
Complete genome sequence and pathogenicity of two swine parainfluenzavirus 3 isolates from pigs in the United States.
  J Virol, 84, 686-694.  
20826610 H.O.Lee, S.J.Zacharek, Y.Xiong, and R.J.Duronio (2010).
Cell type-dependent requirement for PIP box-regulated Cdt1 destruction during S phase.
  Mol Biol Cell, 21, 3639-3653.  
  20885793 H.Xu, J.Wang, Q.Hu, Y.Quan, H.Chen, Y.Cao, C.Li, Y.Wang, and Q.He (2010).
DCAF26, an adaptor protein of Cul4-based E3, is essential for DNA methylation in Neurospora crassa.
  PLoS Genet, 6, 0.  
20544015 M.Liu, E.E.Schmidt, and W.P.Halford (2010).
ICP0 dismantles microtubule networks in herpes simplex virus-infected cells.
  PLoS One, 5, e10975.  
  20937132 N.H.Rosas-Murrieta, I.Herrera-Camacho, H.Palma-Ocampo, G.Santos-López, and J.Reyes-Leyva (2010).
Interaction of mumps virus V protein variants with STAT1-STAT2 heterodimer: experimental and theoretical studies.
  Virol J, 7, 263.  
21135245 S.Yamaji, M.Zhang, J.Zhang, Y.Endo, E.Bibikova, S.P.Goff, and Y.Cang (2010).
Hepatocyte-specific deletion of DDB1 induces liver regeneration and tumorigenesis.
  Proc Natl Acad Sci U S A, 107, 22237-22242.  
19966799 T.Li, E.I.Robert, P.C.van Breugel, M.Strubin, and N.Zheng (2010).
A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.
  Nat Struct Mol Biol, 17, 105-111.
PDB codes: 3i7h 3i7k 3i7l 3i7n 3i7o 3i7p 3i89 3i8c 3i8e
19921174 W.L.Vos, S.Vaughan, P.Y.Lall, J.G.McCaffrey, M.Wysocka-Kapcinska, and J.B.Findlay (2010).
Expression and structural characterization of peripherin/RDS, a membrane protein implicated in photoreceptor outer segment morphology.
  Eur Biophys J, 39, 679-688.  
20395298 X.B.Lv, F.Xie, K.Hu, Y.Wu, L.L.Cao, X.Han, Y.Sang, Y.X.Zeng, and T.Kang (2010).
Damaged DNA-binding protein 1 (DDB1) interacts with Cdh1 and modulates the function of APC/CCdh1.
  J Biol Chem, 285, 18234-18240.  
19694544 A.Ramachandran, and C.M.Horvath (2009).
Paramyxovirus disruption of interferon signal transduction: STATus report.
  J Interferon Cytokine Res, 29, 531-537.  
19404332 F.Randow, and P.J.Lehner (2009).
Viral avoidance and exploitation of the ubiquitin system.
  Nat Cell Biol, 11, 527-534.  
19231300 J.Hannah, and P.Zhou (2009).
Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases.
  DNA Repair (Amst), 8, 536-543.  
  19527883 M.K.Isaacson, and H.L.Ploegh (2009).
Ubiquitination, ubiquitin-like modifiers, and deubiquitination in viral infection.
  Cell Host Microbe, 5, 559-570.  
19386700 M.Puri, K.Lemon, W.P.Duprex, B.K.Rima, and C.M.Horvath (2009).
A point mutation, E95D, in the mumps virus V protein disengages STAT3 targeting from STAT1 targeting.
  J Virol, 83, 6347-6356.  
19818708 M.Zhuang, M.F.Calabrese, J.Liu, M.B.Waddell, A.Nourse, M.Hammel, D.J.Miller, H.Walden, D.M.Duda, S.N.Seyedin, T.Hoggard, J.W.Harper, K.P.White, and B.A.Schulman (2009).
Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.
  Mol Cell, 36, 39-50.
PDB codes: 3hqh 3hqi 3hql 3hqm 3hsv 3htm 3hu6 3hve 3ivq 3ivv
19818632 S.Jackson, and Y.Xiong (2009).
CRL4s: the CUL4-RING E3 ubiquitin ligases.
  Trends Biochem Sci, 34, 562-570.  
19625398 S.Swedan, A.Musiyenko, and S.Barik (2009).
Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways.
  J Virol, 83, 9682-9693.  
18579593 A.Ramachandran, J.P.Parisien, and C.M.Horvath (2008).
STAT2 is a primary target for measles virus V protein-mediated alpha/beta interferon signaling inhibition.
  J Virol, 82, 8330-8338.  
19109893 A.Scrima, R.Konícková, B.K.Czyzewski, Y.Kawasaki, P.D.Jeffrey, R.Groisman, Y.Nakatani, S.Iwai, N.P.Pavletich, and N.H.Thomä (2008).
Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.
  Cell, 135, 1213-1223.
PDB codes: 3ei1 3ei2 3ei3 3ei4
18158581 C.R.Mandel, Y.Bai, and L.Tong (2008).
Protein factors in pre-mRNA 3'-end processing.
  Cell Mol Life Sci, 65, 1099-1122.  
18704118 I.W.Zaidi, G.Rabut, A.Poveda, H.Scheel, J.Malmström, H.Ulrich, K.Hofmann, P.Pasero, M.Peter, and B.Luke (2008).
Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA.
  EMBO Rep, 9, 1034-1040.  
18417591 M.Nishio, J.Ohtsuka, M.Tsurudome, T.Nosaka, and D.Kolakofsky (2008).
Human parainfluenza virus type 2 V protein inhibits genome replication by binding to the L protein: possible role in promoting viral fitness.
  J Virol, 82, 6130-6138.  
18173839 S.Menon, T.Tsuge, N.Dohmae, K.Takio, and N.Wei (2008).
Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome.
  BMC Biochem, 9, 1.  
18363785 S.Wang, J.Liu, Y.Feng, X.Niu, J.Giovannoni, and Y.Liu (2008).
Altered plastid levels and potential for improved fruit nutrient content by downregulation of the tomato DDB1-interacting protein CUL4.
  Plant J, 55, 89.  
18206966 T.Kurz, Y.C.Chou, A.R.Willems, N.Meyer-Schaller, M.L.Hecht, M.Tyers, M.Peter, and F.Sicheri (2008).
Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation.
  Mol Cell, 29, 23-35.
PDB code: 3bq3
19075516 T.Sakaguchi, A.Kato, K.Kiyotani, T.Yoshida, and Y.Nagai (2008).
Studies on the paramyxovirus accessory genes by reverse genetics in the Sendai virus-mouse system.
  Proc Jpn Acad Ser B Phys Biol Sci, 84, 439-451.  
18794354 Y.Fukumoto, N.Dohmae, and F.Hanaoka (2008).
Schizosaccharomyces pombe Ddb1 recruits substrate-specific adaptor proteins through a novel protein motif, the DDB-box.
  Mol Cell Biol, 28, 6746-6756.  
17360488 B.Schröfelbauer, Y.Hakata, and N.R.Landau (2007).
HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1.
  Proc Natl Acad Sci U S A, 104, 4130-4135.  
17349955 C.Schlieker, W.A.Weihofen, E.Frijns, L.M.Kattenhorn, R.Gaudet, and H.L.Ploegh (2007).
Structure of a herpesvirus-encoded cysteine protease reveals a unique class of deubiquitinating enzymes.
  Mol Cell, 25, 677-687.
PDB code: 2j7q
17452440 E.Pick, O.S.Lau, T.Tsuge, S.Menon, Y.Tong, N.Dohmae, S.M.Plafker, X.W.Deng, and N.Wei (2007).
Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes.
  Mol Cell Biol, 27, 4708-4719.  
17630831 J.P.Belzile, G.Duisit, N.Rougeau, J.Mercier, A.Finzi, and E.A.Cohen (2007).
HIV-1 Vpr-Mediated G2 Arrest Involves the DDB1-CUL4A(VPRBP) E3 Ubiquitin Ligase.
  PLoS Pathog, 3, e85.  
17220175 K.Dreher, and J.Callis (2007).
Ubiquitin, hormones and biotic stress in plants.
  Ann Bot, 99, 787-822.  
17325370 K.Hagmaier, N.Stock, B.Precious, K.Childs, L.F.Wang, S.Goodbourn, and R.E.Randall (2007).
Mapuera virus, a rubulavirus that inhibits interferon signalling in a wide variety of mammalian cells without degrading STATs.
  J Gen Virol, 88, 956-966.  
17280619 L.A.Higa, and H.Zhang (2007).
Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy.
  Cell Div, 2, 5.  
17933515 P.Knipscheer, and T.K.Sixma (2007).
Protein-protein interactions regulate Ubl conjugation.
  Curr Opin Struct Biol, 17, 665-673.  
18053699 S.S.Hook, J.J.Lin, and A.Dutta (2007).
Mechanisms to control rereplication and implications for cancer.
  Curr Opin Cell Biol, 19, 663-671.  
17409070 W.M.Al Khateeb, and D.F.Schroeder (2007).
DDB2, DDB1A and DET1 exhibit complex interactions during Arabidopsis development.
  Genetics, 176, 231-242.  
17620334 X.Wen, K.M.Duus, T.D.Friedrich, and C.M.de Noronha (2007).
The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor.
  J Biol Chem, 282, 27046-27057.  
17301228 Y.Cang, J.Zhang, S.A.Nicholas, A.L.Kim, P.Zhou, and S.P.Goff (2007).
DDB1 is essential for genomic stability in developing epidermis.
  Proc Natl Acad Sci U S A, 104, 2733-2737.  
17565698 Y.Kim, and E.T.Kipreos (2007).
Cdt1 degradation to prevent DNA re-replication: conserved and non-conserved pathways.
  Cell Div, 2, 18.  
17145765 Y.Kim, and E.T.Kipreos (2007).
The Caenorhabditis elegans replication licensing factor CDT-1 is targeted for degradation by the CUL-4/DDB-1 complex.
  Mol Cell Biol, 27, 1394-1406.  
16977699 A.G.von Arnim, and C.Schwechheimer (2006).
Life is degrading--thanks to some zomes.
  Mol Cell, 23, 621-629.  
16949367 J.Jin, E.E.Arias, J.Chen, J.W.Harper, and J.C.Walter (2006).
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.
  Mol Cell, 23, 709-721.  
17085042 J.R.Mesters, J.Tan, and R.Hilgenfeld (2006).
Viral enzymes.
  Curr Opin Struct Biol, 16, 776-786.  
16858626 K.Sugasawa (2006).
UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair.
  J Mol Histol, 37, 189-202.  
16987055 M.Chen, and D.Gerlier (2006).
Viral hijacking of cellular ubiquitination pathways as an anti-innate immunity strategy.
  Viral Immunol, 19, 349-362.  
16964240 S.Angers, T.Li, X.Yi, M.J.MacCoss, R.T.Moon, and N.Zheng (2006).
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.
  Nature, 443, 590-593.
PDB code: 2hye
17129780 Y.Cang, J.Zhang, S.A.Nicholas, J.Bastien, B.Li, P.Zhou, and S.P.Goff (2006).
Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells.
  Cell, 127, 929-940.  
17079684 Y.J.He, C.M.McCall, J.Hu, Y.Zeng, and Y.Xiong (2006).
DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.
  Genes Dev, 20, 2949-2954.  
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.

 

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