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11  structures 2828  species 2  interactions 58048  sequences 40  architectures

Family: HTH_1 (PF00126)

Summary: Bacterial regulatory helix-turn-helix protein, lysR family

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 a helix-turn-helix (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. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression. It should not be confused with the helix-loop-helix domain.[1]

Contents

[edit] 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]

[edit] 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]

[edit] 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.

[edit] Tri-helical

The tri-helical helix-turn-helix motif is the simplest helix-turn-helix motif. It consists only of the three main helices. An example of this motif is found in the Transcriptional activator Myb.[9]

[edit] 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.[10] Multihelical versions with additional helices also occur.[11]

[edit] 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.[12][13]

[edit] 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 heli-x-turn-helix with an additional C-terminal alpha helix.[14][8]

[edit] See also

[edit] References

  1. ^ Brennan RG, Matthews BW (1989). "The helix-turn-helix DNA binding motif.". J Biol Chem 264 (4): 1903–6. PMID 2644244. 
  2. ^ a b Matthews BW, Ohlendorf DH, Anderson WF, Takeda Y (1982). "Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor.". Proc Natl Acad Sci U S A 79 (5): 1428–32. PMC 345986. PMID 6951187. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=345986. 
  3. ^ 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. PMID 6452580. 
  4. ^ 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. PMID 6261152. 
  5. ^ Pabo CO, Lewis M (1982). "The operator-binding domain of lambda repressor: structure and DNA recognition.". Nature 298 (5873): 443–7. PMID 7088190. 
  6. ^ a b Wintjens R, Rooman M (1996). "Structural classification of HTH DNA-binding domains and protein-DNA interaction modes.". J Mol Biol 262 (2): 294–313. doi:10.1006/jmbi.1996.0514. PMID 8831795. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8831795. 
  7. ^ 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. PMID 7556672. 
  8. ^ a b Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (2005). "The many faces of the helix-turn-helix domain: transcription regulation and beyond.". FEMS Microbiol Rev 29 (2): 231–62. doi:10.1016/j.femsre.2004.12.008. PMID 15808743. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15808743. 
  9. ^ Ogata K, Hojo H, Aimoto S, Nakai T, Nakamura H, Sarai A et al. (1992). "Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core.". Proc Natl Acad Sci U S A 89 (14): 6428–32. PMC 49514. PMID 1631139. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49514. 
  10. ^ 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. PMID 8153629. 
  11. ^ Iwahara J, Clubb RT (1999). "Solution structure of the DNA binding domain from Dead ringer, a sequence-specific AT-rich interaction domain (ARID).". EMBO J 18 (21): 6084–94. doi:10.1093/emboj/18.21.6084. PMC 1171673. PMID 10545119. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171673. 
  12. ^ Donaldson LW, Petersen JM, Graves BJ, McIntosh LP (1996). "Solution structure of the ETS domain from murine Ets-1: a winged helix-turn-helix DNA binding motif". EMBO J. 15 (1): 125–34. PMC 449924. PMID 8598195. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=449924. 
  13. ^ Sharrocks AD, Brown AL, Ling Y, Yates PR (1997). "The ETS-domain transcription factor family". Int. J. Biochem. Cell Biol. 29 (12): 1371–87. doi:10.1016/S1357-2725(97)00086-1. PMID 9570133. 
  14. ^ Alekshun MN, Levy SB, Mealy TR, Seaton BA, Head JF (2001). "The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution.". Nat Struct Biol 8 (8): 710–4. doi:10.1038/90429. PMID 11473263. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11473263. 

[edit] Further reading

[edit] External links


Protein secondary structure
Protein secondary structure

Helices: α-helix  · 310 helix  · π-helix  · β-helix  · Polyproline helix  · Collagen helix

Extended: β-strand  · Turn  · Beta hairpin  · Beta bulge  · α-strand

Supersecondary: Coiled coil  · Helix-turn-helix  · EF hand
Amino acids

Helix-favoring: Methionine · Alanine · Leucine · Glutamic acid · Glutamine · Lysine

Extended-favoring: Threonine · Isoleucine · Valine · Phenylalanine · Tyrosine · Tryptophan

Disorder-favoring: Glycine · Serine · Proline · Asparagine · Aspartic acid

No preference: Cysteine · Histidine · Arginine

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.

Bacterial regulatory helix-turn-helix protein, lysR family

No Pfam abstract.

Literature references

  1. Tyrrell R, Verschueren KH, Dodson EJ, Murshudov GN, Addy C, Wilkinson AJ; , Structure 1997;5:1017-1032.: The structure of the cofactor-binding fragment of the LysR family member, CysB: a familiar fold with a surprising subunit arrangement. PUBMED:9309218

Clan

This family is a member of clan HTH (CL0123), which has a total of 194 members.

External database links

HOMSTRAD: HTH_1
PANDIT: PF00126
PROSITE: PDOC00043
Pseudofam: PF00126
SCOP: 1al3
SYSTERS: HTH_1

This tab holds annotation information from the InterPro database.

InterPro entry IPR000847

Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis of sequence similarity. One such family, the lysR family, groups together a range of proteins, including ampR, catM, catR, cynR, cysB, gltC, iciA, ilvY, irgB, lysR, metR, mkaC, mleR, nahR, nhaR, nodD, nolR, oxyR, pssR, rbcR, syrM, tcbR, tfdS and trpI [PUBMED:1907267, PUBMED:1592818, PUBMED:1840615, PUBMED:3413113, PUBMED:2034653]. The majority of these proteins appear to be transcription activators and most are known to negatively regulate their own expression. All possess a potential HTH DNA-binding motif towards their N-termini.

Gene Ontology

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

Molecular function sequence-specific DNA binding transcription factor activity (GO:0003700)
Biological process regulation of transcription, DNA-dependent (GO:0006355)

Domain organisation

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

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Pfam Clan

This family is a member of clan HTH (CL0123), which contains the following 194 members:

Arg_repressor B-block_TFIIIC Bac_DnaA_C BetR Bot1p BrkDBD CENP-B_N Cro Crp DDRGK Dimerisation DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2131 DUF2250 DUF2316 DUF3116 DUF3853 DUF387 DUF3908 DUF4095 DUF739 DUF742 DUF977 E2F_TDP ELK Ets Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC Ftsk_gamma FUR GcrA GerE GntR HemN_C Homeobox Homeobox_KN Homez 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_5 HTH_6 HTH_7 HTH_8 HTH_9 HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_OrfB_IS605 HTH_psq HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_IS66 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 IF2_N KorB LacI LexA_DNA_bind LZ_Tnp_IS481 MADF_DNA_bdg MarR MarR_2 Med9 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 Mor MotA_activ MRP-L20 Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-binding Neugrin NUMOD1 OST-HTH PaaX PadR PAX PCI PCI_Csn8 Pencillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_rep_org_N Phage_terminase Pou Pox_D5 PuR_N Put_DNA-bind_N Rap1-DNA-bind Rep_3 RepA_C RepA_N RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RP-C RPA RPA_C RQC Rrf2 RTP SAC3_GANP SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SpoIIID Sulfolobus_pRN TBPIP Terminase_5 TetR_N TFIIE_alpha Tn916-Xis Trans_reg_C TrfA TrmB Trp_repressor UPF0122 z-alpha

Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:
Full length sequences

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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: Prosite
Previous IDs: none
Type: Domain
Author: Sonnhammer ELL
Number in seed: 1556
Number in full: 58048
Average length of the domain: 59.70 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 19.87 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 15929002 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.6 20.6
Noise cut-off 20.5 20.5
Model length: 60
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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

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Interactions

There are 2 interactions for this family. More...

HTH_1 LysR_substrate

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_1 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 seqence.

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