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Gene regulation PDB id
1oqa
Jmol
Contents
Protein chain
110 a.a. *
* Residue conservation analysis
PDB id:
1oqa
Name: Gene regulation
Title: Solution structure of the brct-c domain from human brca1
Structure: Breast cancer type 1 susceptibility protein. Chain: a. Fragment: brct-c. Synonym: brca1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: brca1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 15 models
Authors: O.J.Gaiser,L.J.Ball,P.Schmieder,D.Leitner,H.Strauss,M.Wahl, R.Kuhne,H.Oschkinat,U.Heinemann
Key ref:
O.J.Gaiser et al. (2004). Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1. Biochemistry, 43, 15983-15995. PubMed id: 15609993 DOI: 10.1021/bi049550q
Date:
07-Mar-03     Release date:   15-Jun-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P38398  (BRCA1_HUMAN) -  Breast cancer type 1 susceptibility protein
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1863 a.a.
110 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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: 10.1021/bi049550q Biochemistry 43:15983-15995 (2004)
PubMed id: 15609993  
 
 
Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1.
O.J.Gaiser, L.J.Ball, P.Schmieder, D.Leitner, H.Strauss, M.Wahl, R.Kühne, H.Oschkinat, U.Heinemann.
 
  ABSTRACT  
 
BRCA1 is a tumor suppressor protein associated with breast and ovarian cancer. The C-terminal region of BRCA1 consists of two closely spaced BRCT domains which mediate essential biological functions, including regulation of transcription and control of cell-cycle progression by their interaction with phosphorylated effector proteins. Here we report the NMR structure of the isolated C-terminal BRCT domain (BRCT-c) from human BRCA1. BRCT-c is well-structured in solution, folding independently in the absence of its BRCT-n counterpart. Ultracentrifugation experiments and size exclusion chromatography reveal that BRCT-c exists as a monomer under near-physiological conditions. Dynamics measurements from NMR data show three loops which coincide with the most variable sequence regions in BRCT domains, to be genuinely flexible in solution. The solution structure of BRCT-c shows subtle conformational changes when compared to the crystal structure of BRCT-c in the tandem repeat of BRCA1. These affect sites involved in formation of the BRCT-n-BRCT-c interface and the binding to phosphoserine-containing peptides. The results suggest that the presence of native BRCT-n and a properly aligned BRCT-n-BRCT-c interface are essential if BRCT-c is to adopt a biologically active conformation. Structural consequences of cancer-associated mutations and biological implications of the dynamic behavior are discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20378548 P.J.Rowling, R.Cook, and L.S.Itzhaki (2010).
Toward classification of BRCA1 missense variants using a biophysical approach.
  J Biol Chem, 285, 20080-20087.  
19308666 R.Shin, D.R.Welch, V.K.Mishra, K.T.Nash, D.R.Hurst, and N.Rama Krishna (2009).
Nuclear magnetic resonance and circular dichroism study of metastin (Kisspeptin-54) structure in solution.
  Clin Exp Metastasis, 26, 527-533.  
18582474 C.Xu, L.Wu, G.Cui, M.V.Botuyan, J.Chen, and G.Mer (2008).
Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites.
  J Mol Biol, 381, 361-372.
PDB code: 2k2w
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
18619997 M.S.Cortese, V.N.Uversky, and A.K.Dunker (2008).
Intrinsic disorder in scaffold proteins: getting more from less.
  Prog Biophys Mol Biol, 98, 85.  
18717574 Y.Nominé, M.V.Botuyan, Z.Bajzer, W.G.Owen, A.J.Caride, E.Wasielewski, and G.Mer (2008).
Kinetic analysis of interaction of BRCA1 tandem breast cancer c-terminal domains with phosphorylated peptides reveals two binding conformations.
  Biochemistry, 47, 9866-9879.  
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
16522671 E.Becker, V.Meyer, H.Madaoui, and R.Guerois (2006).
Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response.
  Bioinformatics, 22, 1289-1292.  
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.  
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.