Fig. 1

A–C: The D427 residue is localized in the DNA-binding domain of STAT3 but its atomic coordinates cannot be precisely defined due to the steric flexibility of this region. A Multiple sequence alignments of the regions surrounding D427 residue across the seven STAT family members show STAT1, STAT3, STAT4, and STAT6 to house polar amino acids at homologous positions. B Crystal structure of STAT3 bound to DNA highlighting the region surrounding the mutation D427H and the location of the crucial point mutation F174A (only one protomer is shown). The surrounding region to D427 towards to the amino-terminus is marked in cyan while the region towards the carboxy-terminus is highlighted in orange. Adjacent residues to D427 on either side as well as the F174 residue in the coiled-coil domain are highlighted in magenta. C Crystal structure of an anti-parallel dimer of STAT3 showing the same residues and regions as described above. Structural data were obtained from the Protein Data Bank (pdb) file 4E68 for the parallel STAT3 dimer [8] and 6TLC [11] for the STAT3 anti-parallel dimer, and modified using PyMOL (De Lano Scientific)