2LT7: Solution NMR structure of Kaiso zinc finger DNA binding domain in complex with Kaiso binding site DNA

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.
PDB ID: 2LT7Download
MMDB ID: 102633
PDB Deposition Date: 2012/5/15
Updated in MMDB: 2012/10
Experimental Method:
solution nmr
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 2LT7: trimeric; determined by author
Molecular Components in 2LT7
Label Count Molecule
Protein (1 molecule)
Transcriptional Regulator Kaiso(Gene symbol: ZBTB33)
Molecule annotation
Nucleotides(2 molecules)
DNA (5'-d(*gp*tp*gp*cp*tp*tp*cp*cp*tp*gp*cp*cp*ap*ap*tp*ap*ap*cp*g)-3')
Molecule annotation
DNA (5'-d(*cp*gp*tp*tp*ap*tp*tp*gp*gp*cp*ap*gp*gp*ap*ap*gp*cp*ap*c)-3')
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB