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TALE-likes


Transcription Activator Like Effector Likes (TALE-likes) are a group of bacterial DNA binding proteins named for the first and still best studied group, the TALEs of Xanthomonas bacteria. TALEs are important factors in the plant diseases caused by Xanthomonas bacteria, but are known primarily for their role in biotechnology as programmable DNA binding proteins, particularly in the context of TALE nucleases. TALE-likes have additionally been found in many strains of the Ralstonia solanacearum bacterial species complex, in Burkholderia rhizoxinica strain HKI 454, and in two unknown marine bacteria. Whether or not all these proteins from a single phylogenetic grouping is as yet unclear.

The unifying feature of the TALE-likes are their tandem arrays of DNA binding repeats. These repeats are, with few exceptions, 33-35 amino acids in length, and composed of two alpha-helices on either side of a flexible loop containing the DNA base binding residues and with neighbouring repeats joined by flexible linker loops. Evidence for this common structure comes in part from solved crystal structures of TALEs and a Burkholderia TALE-like, but also from the conservation of the code that all TALE-likes use to recognise DNA-sequences.

TALEs are the first identified, best-studied and largest group within the TALE-likes. TALEs are found throughout the bacterial genus Xanthomonas, comprising mostly plant pathogens. Those TALEs which have been studied have all been shown to be secreted as part of the Type III secretion system into host plant cells. Once inside the host cell they translocate to the nucleus, bind specific DNA sequences within host promoters and turn on downstream genes. Every part of this process is thought to be conserved across all TALEs. The single meaningful difference between individual TALEs, based on current understanding, is the specific DNA sequence that each TALE binds. TALEs from even closely related strains differ in the composition of repeats that make up their DNA binding domain. Repeat composition determines DNA binding preference. In particular position 13 of each repeat confers the DNA base preference of each repeat. During early research it was noted that almost all the differences between repeats of a single TALE repeat array are found in positions 12 and 13 and this finding led to the hypothesis that these residues determine base preference. In fact repeat positions 12 and 13, referred to jointly as the Repeat Variable Diresidue (RVD) are commonly said to confer base specificity despite clear evidence that position 13 is the base determining residue. In addition to the repeat domain TALEs also possess a number of conserved features in the domains flanking the repeats. These include domains for type-III-secretion, nuclear localization and transcriptional activation. This allows TALEs to carry out their biological role as effector proteins secreted into host plant cells to activate expression of specific host genes.


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