3AL3: Crystal Structure Of Topbp1 Brct7/8-bach1 Peptide Complex

The diverse roles of TopBP1 in DNA replication and checkpoint signaling are associated with the scaffolding ability of TopBP1 to initiate various protein-protein interactions. The recognition of the BACH1/FANCJ helicase by TopBP1 is critical for the activation of the DNA replication checkpoint at stalled replication forks and is facilitated by the C-terminal tandem BRCT7/8 domains of TopBP1 and a phosphorylated Thr(1133) binding motif in BACH1. Here we provide the structural basis for this interaction through analysis of the x-ray crystal structures of TopBP1 BRCT7/8 both free and in complex with a BACH1 phospho-peptide. In contrast to canonical BRCT-phospho-peptide recognition, TopBP1 BRCT7/8 undergoes a dramatic conformational change upon BACH1 binding such that the two BRCT repeats pivot about the central BRCT-BRCT interface to provide an extensive and deep peptide-binding cleft. Additionally, we provide the first structural mechanism for Thr(P) recognition among BRCT domains. Together with systematic mutagenesis studies, we highlight the role of key contacts in governing the unique specificity of the TopBP1-BACH1 interaction.
PDB ID: 3AL3Download
MMDB ID: 86570
PDB Deposition Date: 2010/7/22
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 2.15  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3AL3: dimeric; determined by author and by software (PISA)
Molecular Components in 3AL3
Label Count Molecule
Proteins (2 molecules)
DNA Topoisomerase 2-binding Protein 1(Gene symbol: TOPBP1)
Molecule annotation
Peptide of Fanconi Anemia Group J Protein(Gene symbol: BRIP1)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB