3UOT
Crystal Structure of MDC1 FHA Domain in Complex with a Phosphorylated Peptide from the MDC1 N-terminus
Summary for 3UOT
| Entry DOI | 10.2210/pdb3uot/pdb |
| Related | 3UN0 |
| Descriptor | Mediator of DNA damage checkpoint protein 1 (3 entities in total) |
| Functional Keywords | fha domain, dna-damage, mdc1 dimerization, cell cycle |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: Q14676 Q14676 |
| Total number of polymer chains | 4 |
| Total formula weight | 29831.31 |
| Authors | Clapperton, J.A.,Lloyd, J.,Haire, L.F.,Li, J.,Smerdon, S.J. (deposition date: 2011-11-17, release date: 2011-12-28, Last modification date: 2024-10-16) |
| Primary citation | Jungmichel, S.,Clapperton, J.A.,Lloyd, J.,Hari, F.J.,Spycher, C.,Pavic, L.,Li, J.,Haire, L.F.,Bonalli, M.,Larsen, D.H.,Lukas, C.,Lukas, J.,MacMillan, D.,Nielsen, M.L.,Stucki, M.,Smerdon, S.J. The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator. Nucleic Acids Res., 40:3913-3928, 2012 Cited by PubMed Abstract: Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of γH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a 'head-to-tail' dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damage. PubMed: 22234878DOI: 10.1093/nar/gkr1300 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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