3QLC

Complex structure of ATRX ADD domain bound to unmodified H3 1-15 peptide

3QLC の概要

• エントリーDOI: 10.2210/pdb3qlc/pdb
• 関連するPDBエントリー: 3QL9 3QLA 3QLN
• 分子名称: Transcriptional regulator ATRX, peptide of Histone H3.3, ZINC ION, ... (4 entities in total)
• 機能のキーワード: zinc finger, atp-dependent chromatin remodeller, chromatin binding, lysine methylation, nuclear protein, histone-binding protein, transcription-structural protein complex, transcription/structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P46100 P84243
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 33111.79

構造登録者

Li, H.,Patel, D.J. (登録日: 2011-02-02, 公開日: 2011-06-15, 最終更新日: 2023-11-01)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)