Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Cell Cycle Proteins
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Checkpoint Kinase 2
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Humans
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Mice
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Models, Molecular
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Molecular Sequence Data
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Nuclear Proteins / chemistry*
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Nuclear Proteins / metabolism*
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Protein Binding
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Threonine / metabolism*
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Trans-Activators / chemistry*
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Trans-Activators / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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MDC1 protein, human
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Nuclear Proteins
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Trans-Activators
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Threonine
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Checkpoint Kinase 2
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CHEK2 protein, human
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Chek2 protein, mouse
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Protein Serine-Threonine Kinases