Transposons are mobile genetic elements that move from one DNA site to another within their host's genome, often with profound biological consequences. The Mu genome is the largest and most efficient transposon known. The Mu transposase (MuA) is a multidomain protein, which is responsible for translocation of the Mu genome. Mu transposase can be divided into three structurally distinct domains, each with specific functions. The amino– terminal domain (30 kDa) is responsible for sequence–specific DNA binding and can further be subdivided into two separate subdomains, which bind an internal activation sequence (IAS) and the ends of the phage genome, respectively. A highly homologous IAS binding domain is also present in the Mu repressor protein (MuR), but its binding promotes lysogeny of the phage by repressing the expression of genes required for lytic growth and by directly blocking MuA access to the IAS. The IAS binding domains of the MuR and MuA proteins are DNA-binding, winged helix-turn-helix (wHTH) domains of about 75 residues (Mu-type HTH) [1,2].

The Mu-type HTH domain consists of a three-membered α-helical bundle buttressed by a three-stranded antiparallel β-sheet with an overall B1-H1-T-H2-B2-W-B3-H3 topology (where B,H,T and W stand for β-strand, α-helix, turn and wing, repectively (see <PDB:1TNS>). Helices H1 and H2 and the seven-residue turn connecting them comprise a helix-turn-helix (HTH) motif. While the general appearance of the Mu-type DNA-binding domain is similar to that of other winged HTH proteins, the connectivity of the secondary structure elements is permuted. Hence this fold represents a novel class of winged HTH DNA-binding domain [1,2].

Some proteins known to contain a Mu-type HTH domain are listed below:

• Enterobacteria phage Mu (Bacteriophage Mu) transposase (MuA), recombines DNA in the context of several stable higher order nucleoprotein complexes that are built by the assembly of catalytically inactive MuA monomers.
• Enterobacteria phage Mu (Bacteriophage Mu) repressor protein CI.
• Enterobacteria phage D108 (Bacteriophage D108) repressor protein CI.
• Haemophilus influenzae Mu-like prophage FluMu transposase A.

The profile we developed covers the entire Mu-type HTH domain.