2ado
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= MDC1, KIAA0170, NFBD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MDC1, KIAA0170, NFBD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ado FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ado OCA], [http://www.ebi.ac.uk/pdbsum/2ado PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ado RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604801 604801]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: brct repeat]] | [[Category: brct repeat]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:51:11 2008'' |
Revision as of 22:51, 30 March 2008
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| , resolution 1.450Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | MDC1, KIAA0170, NFBD1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure Of The Brct Repeat Region From The Mediator of DNA damage checkpoint protein 1, MDC1
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.
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
Page seeded by OCA on Mon Mar 31 01:51:11 2008
