2LT7

Solution NMR structure of Kaiso zinc finger DNA binding domain in complex with Kaiso binding site DNA

Summary for 2LT7

• Entry DOI: 10.2210/pdb2lt7/pdb
• NMR Information: BMRB: 18462
• Descriptor: Transcriptional regulator Kaiso, DNA (5'-D(*GP*TP*GP*CP*TP*TP*CP*CP*TP*GP*CP*CP*AP*AP*TP*AP*AP*CP*G)-3'), DNA (5'-D(*CP*GP*TP*TP*AP*TP*TP*GP*GP*CP*AP*GP*GP*AP*AP*GP*CP*AP*C)-3'), ... (4 entities in total)
• Functional Keywords: zinc finger, double helix, metal binding protein-dna complex, metal binding protein/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q86T24
• Total number of polymer chains: 3
• Total formula weight: 27933.36

Authors

Buck-Koehntop, B.A.,Stanfield, R.L.,Ekiert, D.C.,Martinez-Yamout, M.A.,Dyson, H.,Wilson, I.A.,Wright, P.E. (deposition date: 2012-05-15, release date: 2012-09-05, Last modification date: 2024-05-01)

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

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

Experimental method

SOLUTION NMR