3QL9: Monoclinic Complex Structure Of Atrx Add Bound To Histone H3k9me3 Peptide

Citation:
Abstract
ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD(ATRX)), whose function has remained elusive. Here we identify ADD(ATRX) as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD(ATRX) bound to H3(1-15)K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.
PDB ID: 3QL9Download
MMDB ID: 91890
PDB Deposition Date: 2011/2/2
Updated in MMDB: 2011/07
Experimental Method:
x-ray diffraction
Resolution: 0.93  Å
Source Organism:
Similar Structures:
Biological Unit for 3QL9: dimeric; determined by author and by software (PISA)
Molecular Components in 3QL9
Label Count Molecule
Proteins (2 molecules)
1
Transcriptional Regulator Atrx(Gene symbol: ATRX)
Molecule annotation
1
Peptide of Histone H3.3(Gene symbol: H3F3A)
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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