(A) CAP (Catabolite Activator Protein, also known as CRP) acts as a transcription promoter by binding at more than 100 sites within the Escherichia coli genome. We rendered the PDB structure 1CGP (Schultz et al. 1991) using Chimera (Huang et al. 1996). (B) The two DNA recognition helices of the CAP homodimer insert themselves into consecutive turns of the major groove. Several consequences can be observed in this CAP binding-site logo. The logo is approximately palindromic, which provides two very similar recognition sites, one for each subunit of the dimer. However, the binding site lacks perfect symmetry, possibly due to the inherent asymmetry of the operon promoter region. The displacement of the two halves is 11 bp, or approximately one full turn of the DNA helix. Additional interactions occur between the protein and the first and last two bases within the DNA minor groove, where the protein cannot easily distinguish A from T, or G from C (Seeman et al. 1976). The data for this logo consists of 59 binding sites determined by DNA footprinting (Robison et al. 1998). (C) The helix-turn-helix motif from the CAP family of homodimeric DNA binding proteins (Brennan and Matthews 1989; Schultz et al. 1991). Positions 180, 181, and 185 are known to interact directly with bases in the major groove (Schultz et al. 1991; Parkinson et al. 1996) and are critical to the sequence-specific binding of the protein. The conserved glycine at position 177 is located inside of the turn between the helices, where packing effects prevent the insertion of a side chain. Partially or completely buried positions (labeled B) frequently contain hydrophobic amino acids, which are colored black. The data for this logo consists of 100 sequences from the full Pfam (Bateman et al. 2002) alignment of this family (Accession no. PF00325). We removed a few sequences with rare insertions for convenience.