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C2H2 Zinc Fingers As DNA Binding Domains

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Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

A great number of C2H2 zinc finger proteins selectively bind to specific DNA sequences and play a critical role in controlling transcription of genes. The specific binding is achieved by zinc finger domains with ββα structure that is formed by tetrahedral binding of Zn2+ ion to the canonical cysteine and histidine residues. Two to three tandem zinc fingers are necessary and sufficient for the specific binding without participation of any other domains. Zinc fingers bind in the major groove of the DNA, wrapping around the strands, with specificity conferred by side chains of several amino acid on the α helices. Some zinc finger proteins undergo homodimerization by hydrophobic interactions or by finger-finger binding and reinforce the specific binding to DNA. Conserved linkers between tandem fingers are necessary for stabilizing the DNA complex. Regulatory mechanisms of zinc finger binding to DNA are emerging. Some cellular factors are found to acetylate and phosphorylate zinc fingers and the linkers of a few proteins. These modifications alter the binding activity of the zinc finger proteins and hence control expression of their target genes. Other factors can methylate promoter regions of genes. This modification alters affinity of zinc finger proteins for the DNA segments and hence controls expression of their target genes.

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Iuchi, S. (2005). C2H2 Zinc Fingers As DNA Binding Domains. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_2

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