The Crystal Structure of TAL Effector PthXo1 Bound to Its DNA Target

Wrapped DNA TAL effectors are proteins that bacterial pathogens inject into plant cells that bind to host DNA to activate expression of plant genes. The DNA-binding domain of TAL proteins is composed of tandem repeats within which a repeat-variable diresidue sequence confers nucleotide specificity. Deng et al. (p. 720, published online 5 January) report the structure of the TAL effector dHax3, containing 11.5 repeats, in DNA-free and DNA-bound states, and Mak et al. (p. 716, published online 5 January) report the structure of the PthXo1 TAL effector, containing 22 repeats, bound to its DNA target. Together, the structures reveal the conformational changes involved in DNA binding and provide the structural basis of DNA recognition. Structures show how a virulence factor in a plant pathogen recognizes and binds to host DNA. DNA recognition by TAL effectors is mediated by tandem repeats, each 33 to 35 residues in length, that specify nucleotides via unique repeat-variable diresidues (RVDs). The crystal structure of PthXo1 bound to its DNA target was determined by high-throughput computational structure prediction and validated by heavy-atom derivatization. Each repeat forms a left-handed, two-helix bundle that presents an RVD-containing loop to the DNA. The repeats self-associate to form a right-handed superhelix wrapped around the DNA major groove. The first RVD residue forms a stabilizing contact with the protein backbone, while the second makes a base-specific contact to the DNA sense strand. Two degenerate amino-terminal repeats also interact with the DNA. Containing several RVDs and noncanonical associations, the structure illustrates the basis of TAL effector–DNA recognition.