2ado

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(New page: 200px<br /> <applet load="2ado" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ado, resolution 1.450&Aring;" /> '''Crystal Structure ...)
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'''Crystal Structure Of The Brct Repeat Region From The Mediator of DNA damage checkpoint protein 1, MDC1'''<br />
'''Crystal Structure Of The Brct Repeat Region From The Mediator of DNA damage checkpoint protein 1, MDC1'''<br />
==Overview==
==Overview==
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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.
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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==
==Disease==
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==About this Structure==
==About this Structure==
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2ADO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2ADO OCA].
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2ADO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ADO OCA].
==Reference==
==Reference==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Edwards, R.A.]]
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[[Category: Edwards, R A.]]
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[[Category: Glover, J.N.]]
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[[Category: Glover, J N.]]
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[[Category: Lee, M.S.]]
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[[Category: Lee, M S.]]
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[[Category: Thede, G.L.]]
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[[Category: Thede, G L.]]
[[Category: brct repeats]]
[[Category: brct repeats]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:49:23 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:18 2008''

Revision as of 14:26, 21 February 2008


2ado, resolution 1.450Å

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

Contents

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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