PDBsum entry: 1gzh

Gene regulation

PDB id: 1gzh

Contents

Protein chains

187 a.a. *

225 a.a. *

196 a.a. *

213 a.a. *

Ligands

SO4 ×2

Metals

_ZN ×2

Waters ×110

* Residue conservation analysis

PDB id:

1gzh

Name:

Gene regulation

Title:

Crystal structure of the brct domains of human 53bp1 bound to the p53 tumor supressor

Structure:

Cellular tumor antigen p53. Chain: a. Fragment: DNA binding region, residues 95-292. Synonym: tumor suppressor p53, phosphoprotein p53, antigen ny-co-13. Engineered: yes. Cellular tumor antigen p53. Chain: c. Fragment: DNA binding region, residues 95-292.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.6Å R-factor: 0.238 R-free: 0.288

Authors:

D.J.Derbyshire,A.J.Doherty

Key ref:

D.J.Derbyshire et al. (2002). Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor. EMBO J, 21, 3863-3872. PubMed id: 12110597 DOI: 10.1093/emboj/cdf383

Date:

22-May-02 Release date: 27-Jun-02

Protein chain

P04637  (P53_HUMAN) -  Cellular tumor antigen p53

Seq: 393 a.a.

Struc: 187 a.a.

Protein chain

Q12888  (TP53B_HUMAN) -  Tumor suppressor p53-binding protein 1

Seq: 1972 a.a.

Struc: 225 a.a.

Protein chain

P04637  (P53_HUMAN) -  Cellular tumor antigen p53

Seq: 393 a.a.

Struc: 196 a.a.

Protein chain

Q12888  (TP53B_HUMAN) -  Tumor suppressor p53-binding protein 1

Seq: 1972 a.a.

Struc: 213 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (2 terms)
• Biological process: apoptosis (2 terms)
• Biochemical function: transcription regulatory region DNA binding (3 terms)

DOI no: 10.1093/emboj/cdf383

EMBO J 21:3863-3872 (2002)

PubMed id: 12110597

Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor.

D.J.Derbyshire, B.P.Basu, L.C.Serpell, W.S.Joo, T.Date, K.Iwabuchi, A.J.Doherty.

ABSTRACT

The BRCT (BRCA1 C-terminus) is an evolutionary conserved protein-protein interacting module found as single, tandem or multiple repeats in a diverse range of proteins known to play roles in the DNA-damage response. The BRCT domains of 53BP1 bind to the tumour suppressor p53. To investigate the nature of this interaction, we have determined the crystal structure of the 53BP1 BRCT tandem repeat in complex with the DNA-binding domain of p53. The structure of the 53BP1-p53 complex shows that the BRCT tandem repeats pack together through a conserved interface that also involves the inter-domain linker. A comparison of the structure of the BRCT region of 53BP1 with the BRCA1 BRCT tandem repeat reveals that the interdomain interface and linker regions are remarkably well conserved. 53BP1 binds to p53 through contacts with the N-terminal BRCT repeat and the inter-BRCT linker. The p53 residues involved in this binding are mutated in cancer and are also important for DNA binding. We propose that BRCT domains bind to cellular target proteins through a conserved structural element termed the 'BRCT recognition motif'.

Selected figure(s)

Figure 1.
Figure 1 Crystal structure of the 53BP1−p53 complex. Structure of the asymmetric unit containing four molecules, two heterodimers (I and II) of p53 DNA-binding domain (brown) in complex with the BRCT tandem repeat of 53BP1 (blue and pink). The heterodimers pack together mainly through contacts made between the N-terminal region of 53BP1. There are no contacts made between the adjacent p53 molecules. The single zinc atom bound to p53 is shown in yellow and the 53BP1 inter-domain linker is shown in green. 'Missing' residues in the structure are denoted by an asterisk.

Figure 5.
Figure 5 A conserved protein binding motif in BRCT domains. (A) Superimposition of the conserved p53-binding motif. This shows a superimposition of the p53-binding interface of 53BP1 (green; residues 1829−1849) with the comparable regions of the BRCT domains of BRCA1 (blue; 1716−1738) and XRCC1 (yellow; 72−94). The C[ ]backbone of these regions overlap with an r.m.s.d. of <1 Å. The position of this motif in relation to p53 binding is also shown (p53 core domain is shown in brown). (B) The highly conserved Trp residue on 3 is positioned in an identical position in all three structures (for clarity only a single Trp is shown) and stacks against the conserved Tyr residue (the superimposed Tyr shown). Two conserved 53BP1−p53 interactions are shown, Arg 248−Leu 1847 and Met 243−Tyr1846.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 3863-3872) copyright 2002.

Figures were selected by the author.