Summary: Helix-turn-helix domain
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Helix-turn-helix Edit Wikipedia article
In proteins, the helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two Î± helices, joined by a short strand of amino acids, that bind to the major groove of DNA. The HTH motif occurs in many proteins that regulate gene expression. It should not be confused with the helixâ€“loopâ€“helix motif.
The discovery of the helix-turn-helix motif was based on similarities between several genes encoding transcription regulatory proteins from bacteriophage lambda and Escherichia coli: Cro, CAP, and Î» repressor, which were found to share a common 20â€“25 amino acid sequence that facilitates DNA recognition.
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 Î± 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 Î± helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition. The recognition helix and its preceding helix always have the same relative orientation.
Classification of helix-turn-helix motifs
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.
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. Multihelical versions with additional helices also occur.
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 Î±1-Î²1-Î²2-Î±2-Î±3-Î²3-Î²4 where the third helix is the DNA recognition helix.
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.
- Brennan RG, Matthews BW (February 1989). "The helix-turn-helix DNA binding motif". The Journal of Biological Chemistry. 264 (4): 1903â€“6. doi:10.1016/S0021-9258(18)94115-3. PMIDÂ 2644244.
- Matthews BW, Ohlendorf DH, Anderson WF, Takeda Y (March 1982). "Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor". Proceedings of the National Academy of Sciences of the United States of America. 79 (5): 1428â€“32. Bibcode:1982PNAS...79.1428M. doi:10.1073/pnas.79.5.1428. PMCÂ 345986. PMIDÂ 6951187.
- Anderson WF, Ohlendorf DH, Takeda Y, Matthews BW (April 1981). "Structure of the cro repressor from bacteriophage lambda and its interaction with DNA". Nature. 290 (5809): 754â€“8. Bibcode:1981Natur.290..754A. doi:10.1038/290754a0. PMIDÂ 6452580. S2CIDÂ 4360799.
- McKay DB, Steitz TA (April 1981). "Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA". Nature. 290 (5809): 744â€“9. doi:10.1038/290744a0. PMIDÂ 6261152. S2CIDÂ 568056.
- Pabo CO, Lewis M (July 1982). "The operator-binding domain of lambda repressor: structure and DNA recognition". Nature. 298 (5873): 443â€“7. Bibcode:1982Natur.298..443P. doi:10.1038/298443a0. PMIDÂ 7088190. S2CIDÂ 39169630.
- Wintjens R, Rooman M (September 1996). "Structural classification of HTH DNA-binding domains and protein-DNA interaction modes". Journal of Molecular Biology. 262 (2): 294â€“313. doi:10.1006/jmbi.1996.0514. PMIDÂ 8831795.
- Suzuki M, Brenner SE (September 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 Letters. 372 (2â€“3): 215â€“21. doi:10.1016/0014-5793(95)00988-L. PMIDÂ 7556672. S2CIDÂ 3037519.
- Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (April 2005). "The many faces of the helix-turn-helix domain: transcription regulation and beyond". FEMS Microbiology Reviews. 29 (2): 231â€“62. doi:10.1016/j.femsre.2004.12.008. PMIDÂ 15808743.
- Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR (May 2007). "The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain". Proceedings of the National Academy of Sciences of the United States of America. 104 (22): 9272â€“7. Bibcode:2007PNAS..104.9272R. doi:10.1073/pnas.0703434104. PMCÂ 1890484. PMIDÂ 17517666.
- Ogata K, Hojo H, Aimoto S, Nakai T, Nakamura H, Sarai A, Ishii S, Nishimura Y (July 1992). "Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core". Proceedings of the National Academy of Sciences of the United States of America. 89 (14): 6428â€“32. Bibcode:1992PNAS...89.6428O. doi:10.1073/pnas.89.14.6428. PMCÂ 49514. PMIDÂ 1631139.
- Hinrichs W, Kisker C, DÃ¼vel M, MÃ¼ller A, Tovar K, Hillen W, Saenger W (April 1994). "Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance". Science. 264 (5157): 418â€“20. Bibcode:1994Sci...264..418H. doi:10.1126/science.8153629. PMIDÂ 8153629.
- Iwahara J, Clubb RT (November 1999). "Solution structure of the DNA binding domain from Dead ringer, a sequence-specific AT-rich interaction domain (ARID)". The EMBO Journal. 18 (21): 6084â€“94. doi:10.1093/emboj/18.21.6084. PMCÂ 1171673. PMIDÂ 10545119.
- Donaldson LW, Petersen JM, Graves BJ, McIntosh LP (January 1996). "Solution structure of the ETS domain from murine Ets-1: a winged helix-turn-helix DNA binding motif". The EMBO Journal. 15 (1): 125â€“34. doi:10.2210/pdb1etc/pdb. PMCÂ 449924. PMIDÂ 8598195.
- Sharrocks AD, Brown AL, Ling Y, Yates PR (December 1997). "The ETS-domain transcription factor family". The International Journal of Biochemistry & Cell Biology. 29 (12): 1371â€“87. doi:10.1016/S1357-2725(97)00086-1. PMIDÂ 9570133.
- Alekshun MN, Levy SB, Mealy TR, Seaton BA, Head JF (August 2001). "The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution". Nature Structural Biology. 8 (8): 710â€“4. doi:10.1038/90429. PMIDÂ 11473263. S2CIDÂ 19608515.
- Struhl K (April 1989). "Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eukaryotic transcriptional regulatory proteins". Trends in Biochemical Sciences. 14 (4): 137â€“40. doi:10.1016/0968-0004(89)90145-X. PMIDÂ 2499084.
- Gajiwala KS, Burley SK (February 2000). "Winged helix proteins". Current Opinion in Structural Biology. 10 (1): 110â€“6. doi:10.1016/S0959-440X(99)00057-3. PMIDÂ 10679470.
- Santos CL, Tavares F, Thioulouse J, Normand P (March 2009). "A phylogenomic analysis of bacterial helix-turn-helix transcription factors". FEMS Microbiology Reviews. 33 (2): 411â€“29. doi:10.1111/j.1574-6976.2008.00154.x. PMIDÂ 19076237.
- Hoskisson PA, Rigali S (2009). "Chapter 1: Variation in form and function the helix-turn-helix regulators of the GntR superfamily". Advances in Applied Microbiology. 69: 1â€“22. doi:10.1016/S0065-2164(09)69001-8. PMIDÂ 19729089.
- Brennan RG (September 1993). "The winged-helix DNA-binding motif: another helix-turn-helix takeoff". Cell. 74 (5): 773â€“6. doi:10.1016/0092-8674(93)90456-Z. PMIDÂ 8374950. S2CIDÂ 31355349.
- Huffman JL, Brennan RG (February 2002). "Prokaryotic transcription regulators: more than just the helix-turn-helix motif". Current Opinion in Structural Biology. 12 (1): 98â€“106. doi:10.1016/s0959-440x(02)00295-6. PMIDÂ 11839496.
Helix-turn-helix domain Provide feedback
The TyrR protein of Haemophilus influenzae is a 36-kD transcription factor whose major function is to control the expression of genes important in the biosynthesis and transport of aromatic amino acids . This entry represents the C-terminal helix-turn-helix DNA-binding domain of TyrR and related proteins.
Internal database links
|SCOOP:||AAA_16 HTH_1 HTH_11 HTH_20 HTH_22 HTH_23 HTH_24 HTH_28 HTH_30 HTH_32 HTH_6 HTH_7 HTH_8 HTH_Tnp_ISL3 MarR MarR_2 Sigma70_r4 Sigma70_r4_2 Terminase_5 TetR_N|
|Similarity to PfamA using HHSearch:||HTH_1 HTH_6 RWP-RK HTH_8 NUMOD1 HTH_23 HTH_AsnC-type HTH_Tnp_ISL3 HTH_38 P22_Cro|
This tab holds annotation information from the InterPro database.
InterPro entry IPR030828
This entry describes the C-terminal DNA-binding helix-turn-helix domain of several regulators of aromatic amino acid metabolism. Examples include TyrR in Escherichia coli and in Haemophilus influenzae, and PhhR in Pseudomonas putida [ PUBMED:9226720 ]. Most members of this family have a sigma-54 interaction domain [ PUBMED:11344327 ]. The TyrR protein of Escherichia coli can act both as a repressor and as an activator of transcription [ PUBMED:15612913 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||DNA binding (GO:0003677)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
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This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.
The clan contains the following 381 members:AbiEi_3_N AbiEi_4 ANAPC2 AphA_like AraR_C Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD BrxA BsuBI_PstI_RE_N C_LFY_FLO CaiF_GrlA CarD_CdnL_TRCF CDC27 Cdc6_C Cdh1_DBD_1 CDT1 CDT1_C CENP-B_N Costars CPSase_L_D3 Cro Crp CSN4_RPN5_eIF3a CSN8_PSD8_EIF3K CtsR Cullin_Nedd8 CUT CUTL CvfB_WH DBD_HTH DDRGK DEP Dimerisation Dimerisation2 DNA_binding_1 DNA_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1376 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2551 DUF2582 DUF3116 DUF3161 DUF3253 DUF3489 DUF3853 DUF3860 DUF3895 DUF3908 DUF433 DUF434 DUF4364 DUF4373 DUF4423 DUF4447 DUF4777 DUF480 DUF4817 DUF5635 DUF573 DUF5805 DUF6088 DUF6262 DUF6362 DUF6432 DUF6462 DUF6471 DUF722 DUF739 DUF742 DUF937 DUF977 E2F_TDP EAP30 eIF-5_eIF-2B ELL ESCRT-II Ets EutK_C Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_D1 FokI_dom_2 Forkhead FtsK_gamma FUR GcrA GerE GntR GP3_package HARE-HTH HemN_C HNF-1_N Homeobox_KN Homeodomain Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_48 HTH_49 HTH_5 HTH_50 HTH_51 HTH_52 HTH_53 HTH_54 HTH_55 HTH_56 HTH_57 HTH_58 HTH_59 HTH_6 HTH_60 HTH_61 HTH_7 HTH_8 HTH_9 HTH_ABP1_N HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_PafC HTH_ParB HTH_psq HTH_SUN2 HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KilA-N Kin17_mid KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MAGE MARF1_LOTUS MarR MarR_2 MC6 MC7 MC8 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 Mrr_N MukE Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NFRKB_winged NOD2_WH NUMOD1 ORC_WH_C OST-HTH P22_Cro PaaX PadR PapB PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_NinH Phage_Nu1 Phage_rep_O Phage_rep_org_N Phage_terminase PheRS_DBD1 PheRS_DBD2 PheRS_DBD3 PhetRS_B1 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N pXO2-72 Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N RepB RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S18 Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RNA_pol_Rpc82 RNase_H2-Ydr279 ROQ_II ROXA-like_wH RP-C RPA RPA_C RPN6_C_helix RQC Rrf2 RTP RuvB_C S10_plectin SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SinI SKA1 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Stn1_C Stork_head Sulfolobus_pRN Suv3_N Swi6_N SWIRM Tau95 TBPIP TEA Terminase_5 TetR_N TFA2_Winged_2 TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB tRNA_bind_2 tRNA_bind_3 Trp_repressor UPF0122 UPF0175 Vir_act_alpha_C XPA_C Xre-like-HTH YdaS_antitoxin YidB YjcQ YokU z-alpha
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Curation and family details
|Number in seed:||5|
|Number in full:||1962|
|Average length of the domain:||48.80 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||9.57 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||4|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the HTH_50 domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
|Protein||Predicted structure||External Information|
|P07604||View 3D Structure||Click here|
|P0A2D7||View 3D Structure||Click here|
|P44694||View 3D Structure||Click here|
|Q9HU19||View 3D Structure||Click here|