3O35

Crystal structure of TRIM24 PHD-Bromo complexed with H3(23-31)K27ac peptide

3O35 の概要

• エントリーDOI: 10.2210/pdb3o35/pdb
• 関連するPDBエントリー: 3O33 3O34 3O36 3O37
• 分子名称: Transcription intermediary factor 1-alpha, Histone H3.1, ZINC ION, ... (4 entities in total)
• 機能のキーワード: trim24, phd finger, bromodomain, h3k27 acetylation, breast cancer, transcription-protein binding complex, transcription/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: O15164 P68431
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 44784.63

構造登録者

Wang, Z.,Patel, D.J. (登録日: 2010-07-23, 公開日: 2010-12-15, 最終更新日: 2024-10-30)

主引用文献

Tsai, W.W.,Wang, Z.,Yiu, T.T.,Akdemir, K.C.,Xia, W.,Winter, S.,Tsai, C.Y.,Shi, X.,Schwarzer, D.,Plunkett, W.,Aronow, B.,Gozani, O.,Fischle, W.,Hung, M.C.,Patel, D.J.,Barton, M.C.
TRIM24 links a non-canonical histone signature to breast cancer.
Nature, 468:927-932, 2010

PubMed Abstract: Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.

PubMed: 21164480
DOI: 10.1038/nature09542

実験手法

X-RAY DIFFRACTION (1.76 Å)