3QLA

Hexagonal complex structure of ATRX ADD bound to H3K9me3 peptide

Summary for 3QLA

• Entry DOI: 10.2210/pdb3qla/pdb
• Related: 3QL9 3QLC 3QLN
• Descriptor: Transcriptional regulator ATRX, peptide of Histone H3.3, ZINC ION, ... (5 entities in total)
• Functional Keywords: zinc finger, transcription, histone, lysine trimethylation, nuclear protein, histone-binding protein, transcription-structural protein complex, transcription/structural protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P46100 P84243
• Total number of polymer chains: 4
• Total formula weight: 33235.04

Authors

Xiang, B.,Li, H. (deposition date: 2011-02-02, release date: 2011-06-15, Last modification date: 2023-11-01)

Primary citation

Iwase, S.,Xiang, B.,Ghosh, S.,Ren, T.,Lewis, P.W.,Cochrane, J.C.,Allis, C.D.,Picketts, D.J.,Patel, D.J.,Li, H.,Shi, Y.
ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome
Nat.Struct.Mol.Biol., 18:769-776, 2011

PubMed 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.

PubMed: 21666679
DOI: 10.1038/nsmb.2062

Experimental method

X-RAY DIFFRACTION (1.6 Å)