PDBsum entry: 1t2u

Antitumor protein

PDB-id: 1t2u

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

207 a.a. *

Ligands

SO4 ×2

Metal ions

_CO

Waters ×51

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1t2u

Name:

Antitumor protein

Title:

Structural basis of phosphopeptide recognition by the brct domain of brca1: structure of brca1 missense variant v1809f

Structure:

Breast cancer type 1 susceptibility protein. Chain: a. Fragment: brct domain 1646-1859. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: brca1. Expressed in: escherichia coli. Expression_system_taxid: 562

UniProt:

P38398 (BRCA1_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

1863 a.a.

Struc:

207 a.a.*

Key:	PfamA domain	PfamB domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

Resolution:

2.80Å

R-factor:

0.277

R-free:

0.294

Authors:

R.S.Williams,M.S.Lee,D.D.Duong,J.N.M.Glover

Key ref:

R.S.Williams et al. (2004). Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.. Nat Struct Mol Biol, 11, 519-525. [PubMed id: 15133503] [DOI: 10.1038/nsmb776]

Date:

22-Apr-04

Release date:

11-May-04

Related entries:

1jnx
1n5o
1t2v

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1038/nsmb776

Nat Struct Mol Biol 11:519-525 (2004)

PubMed id: 15133503

Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.

R.S.Williams, M.S.Lee, D.D.Hau, J.N.Glover.

ABSTRACT

The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.

Selected figure(s)

Figure 1.
Figure 1. Overview of the BRCA1 BRCT -peptide complex. (a) -strands in the BRCT domain are green and -helices are yellow. The peptide is blue. The BRCT residues that recognize the pSer and Phe(+3) residues have transparent surfaces. (b) Amino acid sequence of the human BRCA1 BRCT domain with secondary structure. The residues that contact the phosphoserine are shaded blue, and those that form the Phe(+3)-binding pocket are marked by red circles. Missense mutations assayed for interactions with the peptide are above the sequence. Residues involved in inter-repeat BRCT interactions are boxed. (c) Structural arrangement of one of the three similar dimers in the crystallographic asymmetric unit.

Figure 2.
Figure 2. Details of BRCA1 BRCT -peptide interactions. (a) Stereo view of key residues that recognize the pSer and Phe(+3) residues of the peptide. Hydrogen bonds and salt bridges are indicated by dotted lines. (b) Conformational variability of phosphopeptide binding. Overlay of the five independent peptide structures in the crystallographic asymmetric unit. The BRCT C atoms of each of the BRCT -peptide complexes were superimposed to generate the overlay. (c) Electrostatic surface representation of the BRCT domain with the pSer- and Phe-binding pockets; the peptide is gray.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 519-525) copyright 2004.

Figures were selected by the author.