The helix-turn-helix motif (HTH) is a secondary structural element in proteins . It is part of DNA-binding proteins with a sequence-specific DNA binding domain and consists of two α-helices that are connected by a β- turn (also known as β- turn ). Transcription regulators in bacteria often contain an HTH motif. Homeodomains contain a helix-turn-helix motif.
As a recognition helix, one helix binds in a sequence-specific manner in the major groove of the DNA and enters into several molecular interactions (e.g. hydrogen bonds, ionic bonds and hydrophobic interactions) between amino acids and the bases of the DNA, the other helix positions itself at right angles to it and thus becomes stronger the labile bond with the DNA. Such an arrangement serves, on the one hand, for the stability of the protein-DNA complex, and on the other hand, the specificity of the reaction is increased, since both binding partners must have a very specific spatial structure.
DNA-binding proteins of this type are homodimers or tetramers with a mirror-image symmetrical arrangement of the DNA-binding domain. The centers of the binding domains are 34 Å apart. This length corresponds to the pitch of the DNA, so that the two recognition sequences fit into two successive grooves in the DNA. The binding sequences are palindromes, ie they are made up of two inverted, mirror-inverted sequences with a distance of 11 base pairs , which also corresponds to the pitch of the DNA. As a result, the two recognition sequences lie precisely in successive grooves in the DNA and are thus recognized by the two recognition helices of a dimeric binding protein.
- Georg Fuchs: General Microbiology. 8th edition, Thieme Verlag, ISBN 978-3-13-444608-1 , p. 500.