2ADO

Crystal Structure Of The Brct Repeat Region From The Mediator of DNA damage checkpoint protein 1, MDC1

Summary for 2ADO

• Entry DOI: 10.2210/pdb2ado/pdb
• Descriptor: Mediator of DNA damage checkpoint protein 1 (2 entities in total)
• Functional Keywords: brct repeats, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q14676
• Total number of polymer chains: 2
• Total formula weight: 43019.91

Authors

Lee, M.S.,Edwards, R.A.,Thede, G.L.,Glover, J.N. (deposition date: 2005-07-20, release date: 2005-08-02, Last modification date: 2024-02-14)

Primary citation

Lee, M.S.,Edwards, R.A.,Thede, G.L.,Glover, J.N.
Structure of the BRCT Repeat Domain of MDC1 and Its Specificity for the Free COOH-terminal End of the {gamma}-H2AX Histone Tail.
J.Biol.Chem., 280:32053-32056, 2005

PubMed Abstract: MDC1 (mediator of DNA damage checkpoint protein 1) regulates the recognition and repair of DNA double strand breaks in mammalian cells through its interactions with nuclear foci containing the COOH-terminally phosphorylated form of the histone variant, H2AX. Here we demonstrate that the tandem BRCT repeats of MDC1 directly bind to the phosphorylated tail of H2AX-Ser(P)-Gln-Glu-Tyr, in a manner that is critically dependent on the free carboxylate group of the COOH-terminal Tyr residue. We have determined the x-ray crystal structure of the MDC1 BRCT repeats at 1.45 Angstroms resolution. By a comparison with the structure of the BRCA1 BRCT bound to a phosphopeptide, we suggest that two arginine residues in MDC1, Arg(1932) and Arg(1933) may recognize the COOH terminus of the peptide as well as the penultimate Glu of H2AX, while Gln(2013) may provide additional specificity for the COOH-terminal Tyr.

PubMed: 16049003
DOI: 10.1074/jbc.C500273200

Experimental method

X-RAY DIFFRACTION (1.45 Å)