3UOT: Crystal Structure Of Mdc1 Fha Domain In Complex With A Phosphorylated Peptide From The Mdc1 N-Terminus

Citation:
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 gammaH2AX 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.
PDB ID: 3UOTDownload
MMDB ID: 96142
PDB Deposition Date: 2011/11/17
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3UOT: dimeric; determined by author and by software (PISA)
Molecular Components in 3UOT
Label Count Molecule
Proteins (2 molecules)
1
Mediator of DNA Damage Checkpoint Protein 1(Gene symbol: MDC1)
Molecule annotation
1
Mediator of DNA Damage Checkpoint Protein 1(Gene symbol: MDC1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.