3UN0

Crystal Structure of MDC1 FHA Domain

Summary for 3UN0

• Entry DOI: 10.2210/pdb3un0/pdb
• Descriptor: Mediator of DNA damage checkpoint protein 1, SULFATE ION (3 entities in total)
• Functional Keywords: fha domain, dna-damage, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q14676
• Total number of polymer chains: 2
• Total formula weight: 26011.79

Authors

Clapperton, J.A.,Lloyd, J.,Haire, L.F.,Li, J.,Smerdon, S.J. (deposition date: 2011-11-15, release date: 2011-12-28, Last modification date: 2024-02-28)

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

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: 22234878
DOI: 10.1093/nar/gkr1300

Experimental method

X-RAY DIFFRACTION (2.3 Å)