The HhH motif is a stretch of approximately 20 amino acids that is present in prokaryotic andeukaryotic non-sequence-specific DNA binding proteins [1, 2, 3]. The HhH motif is similar to, but distinct from, the HtH motif. Both of thesemotifs have two helices connected by a short turn. In the HtH motif the secondhelix binds to DNA with the helix in the major groove. This allows the contactbetween specific base and residues throughout the protein. In the HhH motifthe second helix does not protrude from the surface of the protein andtherefore cannot lie in the major groove of the DNA. Crystallographic studiessuggest that the interaction of the HhH domain with DNA is mediated by aminoacids located in the strongly conserved loop (L-P-G-V) and at the N-terminalend of the second helix [4]. This interaction could involve the formation ofhydrogen bonds between protein backbone nitrogens and DNA phosphate groups[4]. The structural difference between the HtH and HhH domains is reflected at thefunctional level: whereas the HtH domain, found primarily in gene regulatoryproteins and binds DNA in a sequence specific manner, the HhH domain is ratherfound in proteins involved in enzymatic activities and binds DNA with nosequence specificity [5].

1. Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. EMBO J. 14, 4108-20
2. Conserved domains in DNA repair proteins and evolution of repair systems. Nucleic Acids Res. 27, 1223-42
3. ComEA is a DNA receptor for transformation of competent Bacillus subtilis. Mol. Microbiol. 31, 271-80
4. The helix-hairpin-helix DNA-binding motif: a structural basis for non-sequence-specific recognition of DNA. Nucleic Acids Res. 24, 2488-97

The HhH motif is a stretch of approximately 20 amino acids that is present in prokaryotic andeuka
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