* [http://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR000047#cite-1 Helix-turn-helix motif, lambda-like repressor], from [[EMBL]]
* [http://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR000047#cite-1 Helix-turn-helix motif, lambda-like repressor], from [[EMBL]]
* [http://www.biochem.arizona.edu/classes/bioc568/PDBfiles/1lmb.pdb Full PDB entry for PDB ID 1LMB]
* [https://web.archive.org/web/20041029023314/http://www.biochem.arizona.edu/classes/bioc568/PDBfiles/1lmb.pdb Full PDB entry for PDB ID 1LMB]
* [http://www.expasy.org/prosite/PDOC50943 Cro/C1-type HTH domain], [http://www.expasy.org/cgi-bin/prosite-search-ful?SEARCH=hth more HTHs] in [[PROSITE]]
* [http://www.expasy.org/prosite/PDOC50943 Cro/C1-type HTH domain], [http://www.expasy.org/cgi-bin/prosite-search-ful?SEARCH=hth more HTHs] in [[PROSITE]]
The helix-turn-helix motif is a DNA-binding motif. The recognition and binding to DNA by helix-turn-helix proteins is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus. In most cases, such as in the Cro repressor, the second helix contributes most to DNA recognition, and hence it is often called the "recognition helix". It binds to the major groove of DNA through a series of hydrogen bonds and various Van der Waals interactions with exposed bases. The other α helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition.[2] The recognition helix and its preceding helix always have the same relative orientation.[6]
Classification of helix-turn-helix motifs
Several attempts have been made to classify the helix-turn-helix motifs based on their structure and the spatial arrangement of their helices.[6][7][8] Some of the main types are described below.
Di-helical
The di-helical helix-turn-helix motif is the simplest helix-turn-helix motif. A fragment of Engrailed homeodomain encompassing only the two helices and the turn was found to be an ultrafast independently folding protein domain.[9]
The tetra-helical helix-turn-helix motif has an additional C-terminal helix compared to the tri-helical motifs. These include the LuxR-type DNA-binding HTH domain found in bacterial transcription factors and the helix-turn-helix motif found in the TetR repressors.[11] Multihelical versions with additional helices also occur.[12]
Winged helix-turn-helix
The winged helix-turn-helix (wHTH) motif is formed by a 3-helical bundle and a 3- or 4-strand beta-sheet (wing). The topology of helices and strands in the wHTH motifs may vary. In the transcription factor ETS wHTH folds into a helix-turn-helix motif on a four-stranded anti-parallel beta-sheet scaffold arranged in the order α1-β1-β2-α2-α3-β3-β4 where the third helix is the DNA recognition helix.[13][14]
Other modified helix-turn-helix motifs
Other derivatives of the helix-turn-helix motif include the DNA-binding domain found in MarR, a regulator of multiple antibiotic resistance, which forms a winged helix-turn-helix with an additional C-terminal alpha helix.[8][15]
^Anderson WF, Ohlendorf DH, Takeda Y, Matthews BW (1981). "Structure of the cro repressor from bacteriophage lambda and its interaction with DNA". Nature. 290 (5809): 754–8. doi:10.1038/290754a0. PMID6452580.
^McKay DB, Steitz TA (1981). "Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA". Nature. 290 (5809): 744–9. doi:10.1038/290744a0. PMID6261152.
^Pabo CO, Lewis M (1982). "The operator-binding domain of lambda repressor: structure and DNA recognition". Nature. 298 (5873): 443–7. doi:10.1038/298443a0. PMID7088190.
^Suzuki M, Brenner SE (1995). "Classification of multi-helical DNA-binding domains and application to predict the DBD structures of sigma factor, LysR, OmpR/PhoB, CENP-B, Rapl, and Xy1S/Ada/AraC". FEBS Lett. 372 (2–3): 215–21. doi:10.1016/0014-5793(95)00988-L. PMID7556672.
^Hinrichs W, Kisker C, Düvel M, Müller A, Tovar K, Hillen W, et al. (1994). "Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance". Science. 264 (5157): 418–20. doi:10.1126/science.8153629. PMID8153629.