Ferguson ZNF Sandbox: Difference between revisions

The DNA-binding motif known as the zinc finger was first discovered by Klug in Transcription Factor IIIA in ''Xenopus laevis'', the African clawed toad.  TFIIIA is a 344 residue protein that contains 9 repeated modules, which are about 30 residues each, that contain <scene name='Zinc_Fingers/Zinc_fingers_cys/3'>two invariant cysteines</scene> and <scene name='Zinc_Fingers/Zinc_fingers_his/4'>two invariant histidines</scene><ref>Voet, Donald; Voet, Judith G.; Pratt, Charlotte W. Fundamentals of Biochemistry: Life at the Molecular Level. 3rd Ed. Hoboken, NJ: Wiley, 2008</ref>.  These are able to bind a zinc ion, allowing the protein to fold tightly around it.  This protein stabilizer is found in thousands of different proteins in both plants and animals, but not in prokaryotic organisms.

In TFIIIA, there are nine consecutive zinc fingers.  Individual zinc fingers can be positioned in both the major groove and across the minor groove of DNA. These results show how TFIIIA can recognize several separated DNA sequences by using fewer fingers than necessary for continuous winding in the major groove.  <scene name='Ferguson_ZNF_Sandbox/1tf6/2'>1tf6</scene> shows a dimer with 6 zinc fingers on each bound to a stretch of DNA.  With this interaction, TFIIIA helps control the transcription of the gene for ribosomal RNA.  The string of zinc fingers curls along the DNA or RNA strands, binding in the grooves and extending amino acids inwards to read the bases. A single zinc finger does not bind very tightly and can only recognize 2 or 3 base pairs, but several can be strung together, causing the group to bind more tightly and allows it to read longer DNA sequences. This modular approach is so appealing that researchers are currently trying to design artificial zinc fingers with different specificities<ref>PMID:2503871</ref>.