4F6N
Crystal structure of Kaiso zinc finger DNA binding protein in complex with methylated CpG site DNA
Summary for 4F6N
Entry DOI | 10.2210/pdb4f6n/pdb |
Related | 4F6M |
Descriptor | 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) |
Functional Keywords | zinc finger, protein-dna complex, double helix, dna binding, dna, dna binding protein-dna complex, dna binding protein/dna |
Biological source | Homo sapiens (human) More |
Cellular location | Nucleus: Q86T24 |
Total number of polymer chains | 3 |
Total formula weight | 28174.64 |
Authors | Buck-Koehntop, B.A.,Stanfield, R.L.,Ekiert, D.C.,Martinez-Yamout, M.A.,Dyson, H.J.,Wilson, I.A.,Wright, P.E. (deposition date: 2012-05-15, release date: 2012-09-05, Last modification date: 2024-04-03) |
Primary citation | 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 Cited by 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: 22949637DOI: 10.1073/pnas.1213726109 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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