3AL2

Crystal Structure of TopBP1 BRCT7/8

Summary for 3AL2

• Entry DOI: 10.2210/pdb3al2/pdb
• Related: 3AL3
• Descriptor: DNA topoisomerase 2-binding protein 1, SULFATE ION (3 entities in total)
• Functional Keywords: brct domain, protein binding, dna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q92547
• Total number of polymer chains: 1
• Total formula weight: 26757.20

Authors

Leung, C.C.,Glover, J.N. (deposition date: 2010-07-22, release date: 2010-12-01, Last modification date: 2017-10-11)

Primary citation

Leung, C.C.,Gong, Z.,Chen, J.,Glover, J.N.
Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control
J.Biol.Chem., 286:4292-4301, 2011

PubMed Abstract: 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.

PubMed: 21127055
DOI: 10.1074/jbc.M110.189555

Experimental method

X-RAY DIFFRACTION (2 Å)