2IG0: Structure Of 53bp1METHYLATED HISTONE PEPTIDE COMPLEX

Citation:
Abstract
Histone lysine methylation has been linked to the recruitment of mammalian DNA repair factor 53BP1 and putative fission yeast homolog Crb2 to DNA double-strand breaks (DSBs), but how histone recognition is achieved has not been established. Here we demonstrate that this link occurs through direct binding of 53BP1 and Crb2 to histone H4. Using X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, we show that, despite low amino acid sequence conservation, both 53BP1 and Crb2 contain tandem tudor domains that interact with histone H4 specifically dimethylated at Lys20 (H4-K20me2). The structure of 53BP1/H4-K20me2 complex uncovers a unique five-residue 53BP1 binding cage, remarkably conserved in the structure of Crb2, that best accommodates a dimethyllysine but excludes a trimethyllysine, thus explaining the methylation state-specific recognition of H4-K20. This study reveals an evolutionarily conserved molecular mechanism of targeting DNA repair proteins to DSBs by direct recognition of H4-K20me2.
PDB ID: 2IG0Download
MMDB ID: 43407
PDB Deposition Date: 2006/9/22
Updated in MMDB: 2007/11
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2IG0: dimeric; determined by author
Molecular Components in 2IG0
Label Count Molecule
Proteins (2 molecules)
1
Tumor Suppressor P53-binding Protein 1(Gene symbol: TP53BP1)
Molecule annotation
1
Dimethylated Histone H4-k20 Peptide
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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