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Structural Delineation of MDC1-FHA Domain Binding with CHK2-pThr68

  作者 Wu, HH; Wu, PY; Huang, KF; Kao, YY; Tsai, MD  
  选自 期刊  Biochemistry;  卷期  2012年51-2;  页码  575-577  
  关联知识点  
 

[摘要]Mammalian MDC1 interacts with CHK2 in the regulation of DNA damage-induced S-phase checkpoint and apoptosis, which is directed by the association of MDC1-FHA and CHK2-pThr68. However, different ligand specificities of MDC1-FHA have been reported, and no structure is available. Here we report the crystal structures of MDC1-FHA and its complex with a CHK2 peptide containing pThr68. Unlike other FHA domains, MDC1-FHA exists as an intrinsic dimer in solution and in crystals. Structural and binding analyses support pThr+3 ligand specificity and provide structural insight into MDC1-CHK2 interaction.

 
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