The HhH motif is a stretch of approximately 20 amino acids that is present in prokaryotic and eukaryotic non-sequence-specific DNA binding proteins [ PUBMED:7664751 PUBMED:9973609 PUBMED:9987128 … expand

The HhH motif is a stretch of approximately 20 amino acids that is present in prokaryotic and eukaryotic non-sequence-specific DNA binding proteins [ PUBMED:7664751 PUBMED:9973609 PUBMED:9987128 ]. The HhH motif is similar to, but distinct from, the HtH motif. Both of these motifs have two helices connected by a short turn. In the HtH motif the second helix binds to DNA with the helix in the major groove. This allows the contact between specific base and residues throughout the protein. In the HhH motif the second helix does not protrude from the surface of the protein and therefore cannot lie in the major groove of the DNA. Crystallographic studies suggest that the interaction of the HhH domain with DNA is mediated by amino acids located in the strongly conserved loop (L-P-G-V) and at the N-terminal end of the second helix [ PUBMED:7664751 ]. This interaction could involve the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups [ PUBMED:8692686 ]. The structural difference between the HtH and HhH domains is reflected at the functional level: whereas the HtH domain, found primarily in gene regulatory proteins and binds DNA in a sequence specific manner, the HhH domain is rather found in proteins involved in enzymatic activities and binds DNA with no sequence specificity [ PUBMED:8692686 ].