Multidomain CTCF bindingfactor in complex to DNA

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CTCF is a crucial multidomain CCCTC binding factor boasting an impressive tandem array of Cys2-His2 coordinated zinc fingers. Among these fingers, most form a highly specific 3-fold base pair interaction known as 'triplets'. These triplets interact directly with the major groove of DNA, thereby modulating the intricate 3D conformation of this protein-DNA complex. A closer examination reveals that zinc fingers 3-7 are primarily responsible for establishing these base-specific hydrogen bonds between amino acid residues and the DNA base pairs. Notably, ZF2 fails to participate in this interaction, while ZF10 and 11 remain invisible in crystallization studies. In contrast, ZF8-9 span the backbone of the DNA duplex without contributing any specific hydrogen bond interactions between bases but do enhance the overall stability of its binding. The remarkable conservation and specificity of these interactions are skillfully compensated by the adaptability of the protein complex to variations from the consensus sequence, as evidenced by the methylation sensitivity of cytosine at position 2 and insensitivity at position 12.