4F6N

Crystal structure of Kaiso zinc finger DNA binding protein in complex with methylated CpG site DNA

4F6N の概要

• エントリーDOI: 10.2210/pdb4f6n/pdb
• 関連するPDBエントリー: 4F6M
• 分子名称: Transcriptional regulator Kaiso, DNA (5'-D(*GP*TP*GP*TP*CP*AP*CP*(5CM)P*GP*(5CM)P*GP*TP*CP*TP*AP*TP*AP*CP*G)-3'), DNA (5'-D(*CP*GP*TP*AP*TP*AP*GP*AP*(5CM)P*GP*(5CM)P*GP*GP*TP*GP*AP*CP*AP*C)-3'), ... (6 entities in total)
• 機能のキーワード: zinc finger, protein-dna complex, double helix, dna binding, dna, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q86T24
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 28174.64

構造登録者

Buck-Koehntop, B.A.,Stanfield, R.L.,Ekiert, D.C.,Martinez-Yamout, M.A.,Dyson, H.J.,Wilson, I.A.,Wright, P.E. (登録日: 2012-05-15, 公開日: 2012-09-05, 最終更新日: 2024-04-03)

主引用文献

Buck-Koehntop, B.A.,Stanfield, R.L.,Ekiert, D.C.,Martinez-Yamout, M.A.,Dyson, H.J.,Wilson, I.A.,Wright, P.E.
Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso.
Proc.Natl.Acad.Sci.USA, 109:15229-15234, 2012

PubMed Abstract: Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys(2)His(2) zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin. Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence.

PubMed: 22949637
DOI: 10.1073/pnas.1213726109

実験手法

X-RAY DIFFRACTION (2.8 Å)