Figure 4.

Sequence conservation in the exposed surface of the BTB dimer. (A) View in the same orientation as in Fig. 2A. (B) View looking directly down the twofold axis of the dimer. A multiple sequence alignment was constructed as follows: residues 6–126 of PLZF were used in a fasta3 (38) search of the swall database (Nonredundant Protein sequence database including Swissprot, Trembl, and TremblNew) at the EMBL- European Bioinformatics Institute server (http://www2.ebi.ac.uk/fasta3). Entries with E score <0.1 were used for further processing. Identical and closely matching sequences were removed from the set, so that the no two pairs in the final set of 42 sequences had >88% sequence identity. The set was then aligned, and the sequence variability was calculated as the number of different amino acids present at each residue position. The sequence variability was then displayed on the solvent accessible surface of the dimer by using grasp (26). In this variability scoring scheme, a fully conserved residue is assigned a value of 1, and the maximum variability is 20. The only exposed, fully conserved residue in the structure is Asp-35, present in the center of the groove.