Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
11  structures 3087  species 1  interaction 5804  sequences 142  architectures

Family: HTH_19 (PF12844)

Summary: Helix-turn-helix domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Helix-turn-helix". More...

Helix-turn-helix Edit Wikipedia article

The λ repressor of bacteriophage lambda employs two helix-turn-helix motifs (left; green) to bind DNA (right; blue and red).

In proteins, the helix-turn-helix (HTH) is a major structural motif capable of binding DNA. In the Figure the λ repressor protein is a dimer. Each monomer incorporates two α 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 helix-loop-helix domain.[1]

Discovery

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 λ repressor, which were found to share a common 20-25 amino acid sequence that facilitates DNA recognition.[2][3][4][5]

Function

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]

Tri-helical

An example of this motif is found in the Transcriptional activator Myb.[10]

Tetra-helical

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]

See also

References

  1. ^ Brennan RG, Matthews BW (February 1989). "The helix-turn-helix DNA binding motif". The Journal of Biological Chemistry. 264 (4): 1903–6. PMID 2644244. 
  2. ^ a b 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): 1428–32. doi:10.1073/pnas.79.5.1428. PMC 345986Freely accessible. PMID 6951187. 
  3. ^ 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): 754–8. doi:10.1038/290754a0. PMID 6452580. 
  4. ^ 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): 744–9. doi:10.1038/290744a0. PMID 6261152. 
  5. ^ Pabo CO, Lewis M (July 1982). "The operator-binding domain of lambda repressor: structure and DNA recognition". Nature. 298 (5873): 443–7. doi:10.1038/298443a0. PMID 7088190. 
  6. ^ a b Wintjens R, Rooman M (September 1996). "Structural classification of HTH DNA-binding domains and protein-DNA interaction modes". Journal of Molecular Biology. 262 (2): 294–313. doi:10.1006/jmbi.1996.0514. PMID 8831795. 
  7. ^ 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 (2-3): 215–21. doi:10.1016/0014-5793(95)00988-L. PMID 7556672. 
  8. ^ a b 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): 231–62. doi:10.1016/j.femsre.2004.12.008. PMID 15808743. 
  9. ^ 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): 9272–7. doi:10.1073/pnas.0703434104. PMC 1890484Freely accessible. PMID 17517666. 
  10. ^ 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): 6428–32. doi:10.1073/pnas.89.14.6428. PMC 49514Freely accessible. PMID 1631139. 
  11. ^ Hinrichs W, Kisker C, Düvel M, Müller A, Tovar K, Hillen W, Saenger W (April 1994). "Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance". Science. 264 (5157): 418–20. doi:10.1126/science.8153629. PMID 8153629. 
  12. ^ 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): 6084–94. doi:10.1093/emboj/18.21.6084. PMC 1171673Freely accessible. PMID 10545119. 
  13. ^ 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): 125–34. doi:10.2210/pdb1etc/pdb. PMC 449924Freely accessible. PMID 8598195. 
  14. ^ 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): 1371–87. doi:10.1016/S1357-2725(97)00086-1. PMID 9570133. 
  15. ^ 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): 710–4. doi:10.1038/90429. PMID 11473263. 

Further reading

  • Struhl K (April 1989). "Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eukaryotic transcriptional regulatory proteins". Trends in Biochemical Sciences. 14 (4): 137–40. doi:10.1016/0968-0004(89)90145-X. PMID 2499084. 
  • Gajiwala KS, Burley SK (February 2000). "Winged helix proteins". Current Opinion in Structural Biology. 10 (1): 110–6. PMID 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): 411–29. doi:10.1111/j.1574-6976.2008.00154.x. PMID 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: 1–22. doi:10.1016/S0065-2164(09)69001-8. PMID 19729089. 
  • Brennan RG (September 1993). "The winged-helix DNA-binding motif: another helix-turn-helix takeoff". Cell. 74 (5): 773–6. doi:10.1016/0092-8674(93)90456-Z. PMID 8374950. 
  • Huffman JL, Brennan RG (February 2002). "Prokaryotic transcription regulators: more than just the helix-turn-helix motif". Current Opinion in Structural Biology. 12 (1): 98–106. doi:10.1016/s0959-440x(02)00295-6. PMID 11839496. 

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Helix-turn-helix domain Provide feedback

Members of this family contains a DNA-binding helix-turn-helix domain. This family contains many example antitoxins from bacterial toxin-antitoxin systems. These antitoxins are likely to be DNA-binding domains.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001387

The cro/C1-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in transcriptional regulators. The domain is named after the transcriptional repressors cro and C1 of temperate bacteriophages 434 and lambda, respectively. Besides in bacteriophages, cro/C1-type regulators are present in prokaryotes and in eukaryotes. The helix-turn-helix DNA-binding motif is generally located in the N-terminal part of these transcriptional regulators. The C-terminal part may contain an oligomerization domain, e.g. C1 repressors and CopR act as dimers, while SinR is a tetramer. The cro/C1-type HTH domain also occurs in combination with the TPR repeat and the C-terminal part of C-5 cytosine-specific DNA methylases contains regions related to the enzymatic function.

Several structures of cro/C1-type transcriptional repressors have been resolved and their DNA-binding domain encompasses five alpha helices, of which the extremities are less conserved [PUBMED:3187531]. The helix-turn-helix motif comprises the second and third helices, the third being called the recognition helix. The HTH is involved in DNA-binding into the major groove, where the recognition helix makes most DNA-contacts. The bacteriophage repressors regulate lysogeny/lytic growth by binding with differential affinity to the operators. These operators show 2-fold symmetry and the repressors bind as dimers. Binding of the repressor to the operator positions the DNA backbone into a slightly bent twist [PUBMED:3187531, PUBMED:11972345].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 340 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD 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_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1819 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2582 DUF3116 DUF3253 DUF3853 DUF3860 DUF3908 DUF433 DUF4364 DUF4423 DUF4447 DUF480 DUF4817 DUF5635 DUF573 DUF722 DUF739 DUF742 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_C FokI_N 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_6 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_ParB HTH_psq HTH_Tnp_1 HTH_Tnp_1_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 MarR MarR_2 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 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 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N 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 RP-C RPA RPA_C 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 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Sulfolobus_pRN Sun2_CC2 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 YdaS_antitoxin YjcQ YokU z-alpha

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(36)
Full
(5804)
Representative proteomes UniProt
(17322)
NCBI
(203103)
Meta
(3009)
RP15
(1387)
RP35
(3869)
RP55
(5881)
RP75
(8539)
Jalview View  View  View  View  View  View  View  View  View 
HTML View                 
PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(36)
Full
(5804)
Representative proteomes UniProt
(17322)
NCBI
(203103)
Meta
(3009)
RP15
(1387)
RP35
(3869)
RP55
(5881)
RP75
(8539)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(36)
Full
(5804)
Representative proteomes UniProt
(17322)
NCBI
(203103)
Meta
(3009)
RP15
(1387)
RP35
(3869)
RP55
(5881)
RP75
(8539)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Jackhmmer:Q180H4
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 36
Number in full: 5804
Average length of the domain: 63.60 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 32.76 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 30.2 30.2
Trusted cut-off 30.2 30.2
Noise cut-off 30.1 30.1
Model length: 65
Family (HMM) version: 7
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

HTH_19

Structures

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_19 domain has been found. There are 11 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.

Loading structure mapping...