3O36

Crystal structure of TRIM24 PHD-Bromo complexed with H4(14-19)K16ac peptide

Summary for 3O36

• Entry DOI: 10.2210/pdb3o36/pdb
• Related: 3O33 3O34 3O35 3O37
• Descriptor: Transcription intermediary factor 1-alpha, Histone H4, ZINC ION, ... (4 entities in total)
• Functional Keywords: trim24, phd finger, bromodomain, h4k16 acetylation, breast cancer, transcription-protein binding complex, transcription/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: O15164 P62805
• Total number of polymer chains: 4
• Total formula weight: 44436.20

Authors

Wang, Z.,Patel, D.J. (deposition date: 2010-07-23, release date: 2010-12-15, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)