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Unknown function PDB id
1l0b
Jmol
Contents
Protein chain
190 a.a. *
Waters ×177
* Residue conservation analysis
PDB id:
1l0b
Name: Unknown function
Title: Crystal structure of rat brca1 tandem-brct region
Structure: Brca1. Chain: a. Fragment: tandem-brct region. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.30Å     R-factor:   not given    
Authors: W.S.Joo,P.D.Jeffrey,S.B.Cantor,M.S.Finnin,D.M.Livingston, N.P.Pavletich
Key ref: W.S.Joo et al. (2002). Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Genes Dev, 16, 583-593. PubMed id: 11877378 DOI: 10.1101/gad.959202
Date:
08-Feb-02     Release date:   20-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O54952  (BRCA1_RAT) -  Breast cancer type 1 susceptibility protein homolog
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1817 a.a.
190 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   2 terms 
  Biological process     DNA repair   1 term 
  Biochemical function     DNA binding     2 terms  

 

 
DOI no: 10.1101/gad.959202 Genes Dev 16:583-593 (2002)
PubMed id: 11877378  
 
 
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure.
W.S.Joo, P.D.Jeffrey, S.B.Cantor, M.S.Finnin, D.M.Livingston, N.P.Pavletich.
 
  ABSTRACT  
 
Brca1 C-terminal (BRCT) domains are a common protein-protein interaction motif in proteins involved in the DNA damage response and DNA repair. The DNA-damage response protein 53BP1 has two BRCT domains that bind to the DNA-binding domain of p53. The 53BP1 tandem-BRCT region is homologous to the tandem-BRCT region of Brca1, which is involved in double-strand break repair and homologous recombination and which binds BACH1, a member of the DEAH helicase family. Here we report the structures of a human 53BP1-p53 complex and of the rat Brca1 BRCT repeats. The 53BP1-p53 structure shows that the two BRCT repeats are arranged tandemly and pack extensively through an interface that also involves the inter-repeat linker. The first BRCT repeat and the linker together bind p53 on a region that overlaps with the DNA-binding surface of p53 and involves p53 residues that are mutated in cancer and are important for DNA binding. Comparison with the structure of the tandem-BRCT region of Brca1 shows a remarkable conservation of the repeat arrangement and of the inter-BRCT repeat interface. Analysis of human BRCA1 tumor-derived mutations and conservation identifies a potential protein-binding site that we show through mutagenesis is involved in BACH1 binding. The BACH1-binding region of Brca1 consists of a unique insertion in the first BRCT repeat and the inter-repeat linker and is analogous to the region of 53BP1 that binds p53.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21635553 R.Naidu, Y.C.Har, and N.A.Taib (2011).
Genetic polymorphisms of TP53-binding protein 1 (TP53BP1) gene and association with breast cancer risk.
  APMIS, 119, 460-467.  
  20516128 A.C.Joerger, and A.R.Fersht (2010).
The tumor suppressor p53: from structures to drug discovery.
  Cold Spring Harb Perspect Biol, 2, a000919.  
  20100603 B.Xue, R.L.Dunbrack, R.W.Williams, A.K.Dunker, and V.N.Uversky (2010).
PONDR-FIT: a meta-predictor of intrinsically disordered amino acids.
  Biochim Biophys Acta, 1804, 996.  
20686496 C.He, H.Nan, A.A.Qureshi, and J.Han (2010).
Genetic variants in the 53BP1 gene and skin cancer risk.
  J Invest Dermatol, 130, 2850-2853.  
20010693 J.H.Lee, A.A.Goodarzi, P.A.Jeggo, and T.T.Paull (2010).
53BP1 promotes ATM activity through direct interactions with the MRN complex.
  EMBO J, 29, 574-585.  
20679332 M.Fromer, and M.Linial (2010).
Exposing the co-adaptive potential of protein-protein interfaces through computational sequence design.
  Bioinformatics, 26, 2266-2272.  
  20862368 T.Ochi, B.L.Sibanda, Q.Wu, D.Y.Chirgadze, V.M.Bolanos-Garcia, and T.L.Blundell (2010).
Structural biology of DNA repair: spatial organisation of the multicomponent complexes of nonhomologous end joining.
  J Nucleic Acids, 2010, 0.  
19286366 A.L.Okorokov, and E.V.Orlova (2009).
Structural biology of the p53 tumour suppressor.
  Curr Opin Struct Biol, 19, 197-202.  
19452558 I.Drikos, G.Nounesis, and C.E.Vorgias (2009).
Characterization of cancer-linked BRCA1-BRCT missense variants and their interaction with phosphoprotein targets.
  Proteins, 77, 464-476.  
19804756 J.Lloyd, J.R.Chapman, J.A.Clapperton, L.F.Haire, E.Hartsuiker, J.Li, A.M.Carr, S.P.Jackson, and S.J.Smerdon (2009).
A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage.
  Cell, 139, 100-111.  
19289498 K.Liu, N.Bellam, H.Y.Lin, B.Wang, C.R.Stockard, W.E.Grizzle, and W.C.Lin (2009).
Regulation of p53 by TopBP1: a potential mechanism for p53 inactivation in cancer.
  Mol Cell Biol, 29, 2673-2693.  
19234526 M.A.Adams-Cioaba, and J.Min (2009).
Structure and function of histone methylation binding proteins.
  Biochem Cell Biol, 87, 93.  
18992264 M.Carvalho, M.A.Pino, R.Karchin, J.Beddor, M.Godinho-Netto, R.D.Mesquita, R.S.Rodarte, D.C.Vaz, V.A.Monteiro, S.Manoukian, M.Colombo, C.B.Ripamonti, R.Rosenquist, G.Suthers, A.Borg, P.Radice, S.A.Grist, A.N.Monteiro, and B.Billack (2009).
Analysis of a set of missense, frameshift, and in-frame deletion variants of BRCA1.
  Mutat Res, 660, 1.  
19473884 M.Lisby, and R.Rothstein (2009).
Choreography of recombination proteins during the DNA damage response.
  DNA Repair (Amst), 8, 1068-1076.  
19656881 S.G.Bailey, E.Verrall, C.Schelcher, A.Rhie, A.J.Doherty, and A.J.Sinclair (2009).
Functional interaction between Epstein-Barr virus replication protein Zta and host DNA damage response protein 53BP1.
  J Virol, 83, 11116-11122.  
19187758 T.Usui, S.S.Foster, and J.H.Petrini (2009).
Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization.
  Mol Cell, 33, 147-159.  
19517458 Y.Naruke, M.Nakashima, K.Suzuki, H.Kondo, T.Hayashi, M.Soda, and I.Sekine (2009).
Genomic instability in the epidermis induced by atomic bomb (A-bomb) radiation: a long-lasting health effect in A-bomb survivors.
  Cancer, 115, 3782-3790.  
  19558684 Y.Tan, and R.Luo (2009).
Structural and functional implications of p53 missense cancer mutations.
  PMC Biophys, 2, 5.  
18410249 A.C.Joerger, and A.R.Fersht (2008).
Structural biology of the tumor suppressor p53.
  Annu Rev Biochem, 77, 557-582.  
18579587 A.Kumar, W.S.Joo, G.Meinke, S.Moine, E.N.Naumova, and P.A.Bullock (2008).
Evidence for a structural relationship between BRCT domains and the helicase domains of the replication initiators encoded by the Polyomaviridae and Papillomaviridae families of DNA tumor viruses.
  J Virol, 82, 8849-8862.  
18366598 C.J.Oldfield, J.Meng, J.Y.Yang, M.Q.Yang, V.N.Uversky, and A.K.Dunker (2008).
Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners.
  BMC Genomics, 9, S1.  
18647606 E.Eryilmaz, J.Benach, M.Su, J.Seetharaman, K.Dutta, H.Wei, P.Gottlieb, J.F.Hunt, and R.Ghose (2008).
Structure and dynamics of the P7 protein from the bacteriophage phi 12.
  J Mol Biol, 382, 402-422.
PDB code: 2q82
17453335 I.Konstantopoulou, T.Rampias, A.Ladopoulou, G.Koutsodontis, S.Armaou, T.Anagnostopoulos, G.Nikolopoulos, S.Kamakari, G.Nounesis, A.Stylianakis, C.Karanikiotis, E.Razis, H.Gogas, A.Keramopoulos, V.Gaki, C.Markopoulos, D.Skarlos, N.Pandis, T.Bei, I.Arzimanoglou, G.Fountzilas, and D.Yannoukakos (2008).
Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients.
  Breast Cancer Res Treat, 107, 431-441.  
18285658 J.Kobayashi, K.Iwabuchi, K.Miyagawa, E.Sonoda, K.Suzuki, M.Takata, and H.Tauchi (2008).
Current topics in DNA double-strand break repair.
  J Radiat Res (Tokyo), 49, 93.  
17985346 M.Nakashima, K.Suzuki, S.Meirmanov, Y.Naruke, M.Matsuu-Matsuyama, K.Shichijo, V.Saenko, H.Kondo, T.Hayashi, M.Ito, S.Yamashita, and I.Sekine (2008).
Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis.
  Int J Cancer, 122, 1082-1088.  
  19043619 R.Karchin, M.Agarwal, A.Sali, F.Couch, and M.S.Beattie (2008).
Classifying Variants of Undetermined Significance in BRCA2 with Protein Likelihood Ratios.
  Cancer Inform, 6, 203-216.  
17902052 T.Anagnostopoulos, M.Pertesi, I.Konstantopoulou, S.Armaou, S.Kamakari, G.Nasioulas, A.Athanasiou, A.Dobrovic, M.A.Young, D.Goldgar, G.Fountzilas, and D.Yannoukakos (2008).
G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history.
  Breast Cancer Res Treat, 110, 377-385.  
18380789 Y.Naruke, M.Nakashima, K.Suzuki, M.Matsuu-Matsuyama, K.Shichijo, H.Kondo, and I.Sekine (2008).
Alteration of p53-binding protein 1 expression during skin carcinogenesis: association with genomic instability.
  Cancer Sci, 99, 946-951.  
18452305 Y.Shen, and L.Tong (2008).
Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho-peptide from human ACC1.
  Biochemistry, 47, 5767-5773.
PDB code: 3coj
18485870 Y.Tang, W.Zhao, Y.Chen, Y.Zhao, and W.Gu (2008).
Acetylation is indispensable for p53 activation.
  Cell, 133, 612-626.  
17401432 A.C.Joerger, and A.R.Fersht (2007).
Structure-function-rescue: the diverse nature of common p53 cancer mutants.
  Oncogene, 26, 2226-2242.  
  17505536 A.Hoshino, C.J.Yee, M.Campbell, R.L.Woltjer, R.L.Townsend, R.van der Meer, Y.Shyr, J.T.Holt, H.L.Moses, and R.A.Jensen (2007).
Effects of BRCA1 transgene expression on murine mammary gland development and mutagen-induced mammary neoplasia.
  Int J Biol Sci, 3, 281-291.  
17452983 A.R.Clarke, N.Jones, F.Pryde, Y.Adachi, and O.J.Sansom (2007).
53BP1 deficiency in intestinal enterocytes does not alter the immediate response to ionizing radiation, but leads to increased nuclear area consistent with polyploidy.
  Oncogene, 26, 6349-6355.  
17063491 C.A.Gough, T.Gojobori, and T.Imanishi (2007).
Cancer-related mutations in BRCA1-BRCT cause long-range structural changes in protein-protein binding sites: a molecular dynamics study.
  Proteins, 66, 69-86.  
17915942 E.F.DeRose, M.W.Clarkson, S.A.Gilmore, C.J.Galban, A.Tripathy, J.M.Havener, G.A.Mueller, D.A.Ramsden, R.E.London, and A.L.Lee (2007).
Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining.
  Biochemistry, 46, 12100-12110.
PDB code: 2htf
17308087 M.A.Carvalho, S.M.Marsillac, R.Karchin, S.Manoukian, S.Grist, R.F.Swaby, T.P.Urmenyi, E.Rondinelli, R.Silva, L.Gayol, L.Baumbach, R.Sutphen, J.L.Pickard-Brzosowicz, K.L.Nathanson, A.Sali, D.Goldgar, F.J.Couch, P.Radice, and A.N.Monteiro (2007).
Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis.
  Cancer Res, 67, 1494-1501.  
17189298 M.Hölzel, T.Grimm, M.Rohrmoser, A.Malamoussi, T.Harasim, A.Gruber-Eber, E.Kremmer, and D.Eick (2007).
The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA processing.
  Nucleic Acids Res, 35, 789-800.  
17561994 P.Vasickova, E.Machackova, M.Lukesova, J.Damborsky, O.Horky, H.Pavlu, J.Kuklova, V.Kosinova, M.Navratilova, and L.Foretova (2007).
High occurrence of BRCA1 intragenic rearrangements in hereditary breast and ovarian cancer syndrome in the Czech Republic.
  BMC Med Genet, 8, 32.  
17305420 R.Karchin, A.N.Monteiro, S.V.Tavtigian, M.A.Carvalho, and A.Sali (2007).
Functional impact of missense variants in BRCA1 predicted by supervised learning.
  PLoS Comput Biol, 3, e26.  
17015838 A.C.Joerger, H.C.Ang, and A.R.Fersht (2006).
Structural basis for understanding oncogenic p53 mutations and designing rescue drugs.
  Proc Natl Acad Sci U S A, 103, 15056-15061.
PDB codes: 2j1w 2j1x 2j1y 2j1z 2j20 2j21
16547092 C.Gabrielse, C.T.Miller, K.H.McConnell, A.DeWard, C.A.Fox, and M.Weinreich (2006).
A Dbf4p BRCA1 C-terminal-like domain required for the response to replication fork arrest in budding yeast.
  Genetics, 173, 541-555.  
17094803 D.C.Zappulla, A.S.Maharaj, J.J.Connelly, R.A.Jockusch, and R.Sternglanz (2006).
Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs.
  BMC Mol Biol, 7, 40.  
16498444 G.Trigiante, and X.Lu (2006).
ASPP [corrected] and cancer.
  Nat Rev Cancer, 6, 217-226.  
17043355 I.Ward, J.E.Kim, K.Minn, C.C.Chini, G.Mer, and J.Chen (2006).
The tandem BRCT domain of 53BP1 is not required for its repair function.
  J Biol Chem, 281, 38472-38477.  
17161371 J.Liu, Y.Pan, B.Ma, and R.Nussinov (2006).
"Similarity trap" in protein-protein interactions could be carcinogenic: simulations of p53 core domain complexed with 53BP1 and BRCA1 BRCT domains.
  Structure, 14, 1811-1821.  
16793544 M.Kitayner, H.Rozenberg, N.Kessler, D.Rabinovich, L.Shaulov, T.E.Haran, and Z.Shakked (2006).
Structural basis of DNA recognition by p53 tetramers.
  Mol Cell, 22, 741-753.
PDB codes: 2ac0 2ady 2ahi 2ata
16945145 M.M.Adams, and P.B.Carpenter (2006).
Tying the loose ends together in DNA double strand break repair with 53BP1.
  Cell Div, 1, 19.  
16397295 N.Lévy, A.Martz, A.Bresson, C.Spenlehauer, G.de Murcia, and J.Ménissier-de Murcia (2006).
XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage.
  Nucleic Acids Res, 34, 32-41.  
16951253 W.Lilyestrom, M.G.Klein, R.Zhang, A.Joachimiak, and X.S.Chen (2006).
Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor.
  Genes Dev, 20, 2373-2382.
PDB code: 2h1l
15576564 B.A.Joughin, B.Tidor, and M.B.Yaffe (2005).
A computational method for the analysis and prediction of protein:phosphopeptide-binding sites.
  Protein Sci, 14, 131-139.  
16204849 B.Ma, Y.Pan, K.Gunasekaran, O.Keskin, R.B.Venkataraghavan, A.J.Levine, and R.Nussinov (2005).
The contribution of the Trp/Met/Phe residues to physical interactions of p53 with cellular proteins.
  Phys Biol, 2, S56-S66.  
16260621 I.M.Ward, S.Difilippantonio, K.Minn, M.D.Mueller, J.R.Molina, X.Yu, C.S.Frisk, T.Ried, A.Nussenzweig, and J.Chen (2005).
53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice.
  Mol Cell Biol, 25, 10079-10086.  
16377563 M.Stucki, J.A.Clapperton, D.Mohammad, M.B.Yaffe, S.J.Smerdon, and S.P.Jackson (2005).
MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.
  Cell, 123, 1213-1226.
PDB code: 2azm
14978302 C.M.Ekblad, A.Friedler, D.Veprintsev, R.L.Weinberg, and L.S.Itzhaki (2004).
Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis.
  Protein Sci, 13, 617-625.  
15341721 G.Charier, J.Couprie, B.Alpha-Bazin, V.Meyer, E.Quéméneur, R.Guérois, I.Callebaut, B.Gilquin, and S.Zinn-Justin (2004).
The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding.
  Structure, 12, 1551-1562.
PDB code: 1ssf
15133502 J.A.Clapperton, I.A.Manke, D.M.Lowery, T.Ho, L.F.Haire, M.B.Yaffe, and S.J.Smerdon (2004).
Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.
  Nat Struct Mol Biol, 11, 512-518.
PDB code: 1t15
15501676 J.N.Glover, R.S.Williams, and M.S.Lee (2004).
Interactions between BRCT repeats and phosphoproteins: tangled up in two.
  Trends Biochem Sci, 29, 579-585.  
15133503 R.S.Williams, M.S.Lee, D.D.Hau, and J.N.Glover (2004).
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.
  Nat Struct Mol Biol, 11, 519-525.
PDB codes: 1t2u 1t2v
14739927 S.Mochida, F.Esashi, N.Aono, K.Tamai, M.J.O'Connell, and M.Yanagida (2004).
Regulation of checkpoint kinases through dynamic interaction with Crb2.
  EMBO J, 23, 418-428.  
12640136 I.M.Ward, K.Minn, J.van Deursen, and J.Chen (2003).
p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice.
  Mol Cell Biol, 23, 2556-2563.  
  12537518 J.Qin, and L.Li (2003).
Molecular anatomy of the DNA damage and replication checkpoints.
  Radiat Res, 159, 139-148.  
14576410 K.W.Caldecott (2003).
Cell signaling. The BRCT domain: signaling with friends?
  Science, 302, 579-580.  
12110597 D.J.Derbyshire, B.P.Basu, L.C.Serpell, W.S.Joo, T.Date, K.Iwabuchi, and A.J.Doherty (2002).
Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor.
  EMBO J, 21, 3863-3872.
PDB code: 1gzh
12351827 D.J.Derbyshire, B.P.Basu, T.Date, K.Iwabuchi, and A.J.Doherty (2002).
Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor.
  Acta Crystallogr D Biol Crystallogr, 58, 1826-1829.  
12419185 J.Kobayashi, H.Tauchi, S.Sakamoto, A.Nakamura, K.Morishima, S.Matsuura, T.Kobayashi, K.Tamai, K.Tanimoto, and K.Komatsu (2002).
NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain.
  Curr Biol, 12, 1846-1851.  
12124396 L.O.Hansson, A.Friedler, S.Freund, S.Rudiger, and A.R.Fersht (2002).
Two sequence motifs from HIF-1alpha bind to the DNA-binding site of p53.
  Proc Natl Acad Sci U S A, 99, 10305-10309.  
12461529 R.T.Abraham (2002).
Checkpoint signalling: focusing on 53BP1.
  Nat Cell Biol, 4, E277-E279.  
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.