6HM3

Crystal structure of Rad4 BRCT1,2 in complex with a Sld3 phosphopeptide

Summary for 6HM3

• Entry DOI: 10.2210/pdb6hm3/pdb
• Descriptor: S-M checkpoint control protein rad4, DNA replication regulator sld3, GLYCEROL, ... (5 entities in total)
• Functional Keywords: brct domain phosphopeptide recognition, cell cycle
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); More
• Total number of polymer chains: 2
• Total formula weight: 24912.44

Authors

Day, M.,Rappas, M.,Oliver, A.W.,Pearl, L.H. (deposition date: 2018-09-12, release date: 2018-10-17, Last modification date: 2024-11-06)

Primary citation

Day, M.,Rappas, M.,Ptasinska, K.,Boos, D.,Oliver, A.W.,Pearl, L.H.
BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands.
Elife, 7:-, 2018

PubMed Abstract: TOPBP1 and its fission yeast homologueRad4, are critical players in a range of DNA replication, repair and damage signalling processes. They are composed of multiple BRCT domains, some of which bind phosphorylated motifs in other proteins. They thus act as multi-point adaptors bringing proteins together into functional combinations, dependent on post-translational modifications downstream of cell cycle and DNA damage signals. We have now structurally and/or biochemically characterised a sufficient number of high-affinity complexes for the conserved N-terminal region of TOPBP1 and Rad4 with diverse phospho-ligands, including human RAD9 and Treslin, and Crb2 and Sld3, to define the determinants of BRCT domain specificity. We use this to identify and characterise previously unknown phosphorylation-dependent TOPBP1/Rad4-binding motifs in human RHNO1 and the fission yeast homologue of MDC1, Mdb1. These results provide important insights into how multiple BRCT domains within TOPBP1/Rad4 achieve selective and combinatorial binding of their multiple partner proteins.

PubMed: 30295604
DOI: 10.7554/eLife.39979

Experimental method

X-RAY DIFFRACTION (1.77263620528 Å)