2azm
From Proteopedia
(New page: 200px<br /> <applet load="2azm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2azm, resolution 2.41Å" /> '''Crystal structure o...) |
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| - | [[Image:2azm.gif|left|200px]]<br /> | + | [[Image:2azm.gif|left|200px]]<br /><applet load="2azm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2azm" size=" | + | |
caption="2azm, resolution 2.41Å" /> | caption="2azm, resolution 2.41Å" /> | ||
'''Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX'''<br /> | '''Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Histone variant H2AX phosphorylation in response to DNA damage is the | + | Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AZM 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:// | + | 2AZM 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=2AZM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Clapperton, J | + | [[Category: Clapperton, J A.]] |
| - | [[Category: Jackson, S | + | [[Category: Jackson, S P.]] |
[[Category: Mohammad, D.]] | [[Category: Mohammad, D.]] | ||
| - | [[Category: Smerdon, S | + | [[Category: Smerdon, S J.]] |
[[Category: Stucki, M.]] | [[Category: Stucki, M.]] | ||
| - | [[Category: Yaffe, M | + | [[Category: Yaffe, M B.]] |
[[Category: brct repeat]] | [[Category: brct repeat]] | ||
[[Category: dna damage]] | [[Category: dna damage]] | ||
[[Category: protein-phosphopeptide complex]] | [[Category: protein-phosphopeptide complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:38 2008'' |
Revision as of 14:32, 21 February 2008
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Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX
Contents |
Overview
Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage.
Disease
Known disease associated with this structure: Muscular dystrophy, congenital, 1B OMIM:[604801]
About this Structure
2AZM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks., Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP, Cell. 2005 Dec 29;123(7):1213-26. PMID:16377563
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