2ado

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spinqualitylabelsall models 2ado, resolution 1.450Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known disease associated with this structure: Muscular dystrophy, congenital, 1B OMIM:[604801]

About this Structure

2ADO is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the BRCT repeat domain of MDC1 and its specificity for the free COOH-terminal end of the gamma-H2AX histone tail., Lee MS, Edwards RA, Thede GL, Glover JN, J Biol Chem. 2005 Sep 16;280(37):32053-6. Epub 2005 Jul 27. PMID:16049003

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