A Simple Cipher Governs DNA Recognition by TAL Effectors

TAL Order Xanthomonas bacteria attack their plant hosts by delivering their own transcription-activator–like (TAL) proteins into the plant cell nucleus and alter the plant's gene regulation (see the Perspective by Voytas and Joung). Moscou and Bogdanove (p. 1501, published online 29 October: see the cover) and Boch et al. (p. 1509, published online 29 October) have now discovered how the similar but not identical repeats in the TAL proteins encode the specificity needed for the proteins to find their targets. Each repeat is specific for one DNA base pair, a specificity encoded by hypervariable amino acid positions. Combining several repeats with different amino acids in the hypervariable positions allowed the production of new effectors that targeted new DNA sites. Xanthomonas bacteria use an amino acid–based code to target effector molecules to specific DNA sequences. TAL effectors of plant pathogenic bacteria in the genus Xanthomonas bind host DNA and activate genes that contribute to disease or turn on defense. Target specificity depends on an effector-variable number of typically 34 amino acid repeats, but the mechanism of recognition is not understood. We show that a repeat-variable pair of residues specifies the nucleotides in the target site, one pair to one nucleotide, with no apparent context dependence. Our finding represents a previously unknown mechanism for protein-DNA recognition that explains TAL effector specificity, enables target site prediction, and opens prospects for use of TAL effectors in research and biotechnology.