5U6K

Crystal structure of TopBP1 BRCT4/5 in complex with a BLM phosphopeptide

Summary for 5U6K

• Entry DOI: 10.2210/pdb5u6k/pdb
• Descriptor: DNA topoisomerase 2-binding protein 1, Bloom Sydrome recQ helicase like protein (BLM) (2 entities in total)
• Functional Keywords: brct repeat family replication checkpoint control peptide bound protein complex, peptide binding protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 12
• Total formula weight: 179706.34

Authors

Glover, J.N.M.,Sun, L.,Edwards, R.A. (deposition date: 2016-12-08, release date: 2017-10-04, Last modification date: 2024-10-23)

Primary citation

Sun, L.,Huang, Y.,Edwards, R.A.,Yang, S.,Blackford, A.N.,Niedzwiedz, W.,Glover, J.N.M.
Structural Insight into BLM Recognition by TopBP1.
Structure, 25:1582-1588.e3, 2017

PubMed Abstract: Topoisomerase IIβ binding protein 1 (TopBP1) is a critical protein-protein interaction hub in DNA replication checkpoint control. It was proposed that TopBP1 BRCT5 interacts with Bloom syndrome helicase (BLM) to regulate genome stability through either phospho-Ser304 or phospho-Ser338 of BLM. Here we show that TopBP1 BRCT5 specifically interacts with the BLM region surrounding pSer304, not pSer338. Our crystal structure of TopBP1 BRCT4/5 bound to BLM reveals recognition of pSer304 by a conserved pSer-binding pocket, and interactions between an FVPP motif N-terminal to pSer304 and a hydrophobic groove on BRCT5. This interaction utilizes the same surface of BRCT5 that recognizes the DNA damage mediator, MDC1; however the binding orientations of MDC1 and BLM are reversed. While the MDC1 interactions are largely electrostatic, the interaction with BLM has higher affinity and relies on a mix of electrostatics and hydrophobicity. We suggest that similar evolutionarily conserved interactions may govern interactions between TopBP1 and 53BP1.

PubMed: 28919440
DOI: 10.1016/j.str.2017.08.005

Experimental method

X-RAY DIFFRACTION (2.6 Å)