2J2S

Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase

2J2S の概要

• エントリーDOI: 10.2210/pdb2j2s/pdb
• 関連するPDBエントリー: 2AGH
• 分子名称: ZINC FINGER PROTEIN HRX, ZINC ION (2 entities in total)
• 機能のキーワード: transcription regulation, chromosomal rearrangement, zinc-finger, dna-binding, bromodomain, polymorphism, mixed lineage leukaemia, zinc binding, transcription, metal-binding, zinc, cxxc, mbd1, hox genes, chromatin, methylation, proto-oncogene, nuclear protein, phosphorylation, cpg dinucleotide, alternative splicing
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus . MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8197.48

構造登録者

Allen, M.D.,Grummitt, C.G.,Hilcenko, C.,Young-Min, S.,Tonkin, L.M.,Johnson, C.M.,Bycroft, M.,Warren, A.J. (登録日: 2006-08-17, 公開日: 2006-08-21, 最終更新日: 2024-05-15)

主引用文献

Allen, M.D.,Grummitt, C.G.,Hilcenko, C.,Min, S.Y.,Tonkin, L.M.,Johnson, C.M.,Freund, S.M.,Bycroft, M.,Warren, A.J.
Solution Structure of the Nonmethyl-Cpg-Binding Cxxc Domain of the Leukaemia-Associated Mll Histone Methyltransferase
Embo J., 25:4503-, 2006

PubMed Abstract: Methylation of CpG dinucleotides is the major epigenetic modification of mammalian genomes, critical for regulating chromatin structure and gene activity. The mixed-lineage leukaemia (MLL) CXXC domain selectively binds nonmethyl-CpG DNA, and is required for transformation by MLL fusion proteins that commonly arise from recurrent chromosomal translocations in infant and secondary treatment-related acute leukaemias. To elucidate the molecular basis of nonmethyl-CpG DNA recognition, we determined the structure of the human MLL CXXC domain by multidimensional NMR spectroscopy. The CXXC domain has a novel fold in which two zinc ions are each coordinated tetrahedrally by four conserved cysteine ligands provided by two CGXCXXC motifs and two distal cysteine residues. We have identified the CXXC domain DNA binding interface by means of chemical shift perturbation analysis, cross-saturation transfer and site-directed mutagenesis. In particular, we have shown that residues in an extended surface loop are in close contact with the DNA. These data provide a template for the design of specifically targeted therapeutics for poor prognosis MLL-associated leukaemias.

PubMed: 16990798
DOI: 10.1038/SJ.EMBOJ.7601340

実験手法

SOLUTION NMR