2azm
From Proteopedia
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Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX
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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
Page seeded by OCA on Thu Feb 21 16:32:38 2008
