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94  structures 2588  species 3  interactions 3362  sequences 14  architectures

Family: Fe_dep_repress (PF01325)

Summary: Iron dependent repressor, N-terminal DNA binding domain

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Iron dependent repressor Edit Wikipedia article

Iron dependent repressor, N-terminal DNA binding domain (dtxR-type HTH domain)
PDB 1u8r EBI.jpg
crystal structure of an ider-dna complex reveals a conformational change in activated ider for base-specific interactions
Identifiers
Symbol Fe_dep_repress
Pfam PF01325
Pfam clan CL0123
InterPro IPR022687
SCOP 2dtr
SUPERFAMILY 2dtr
Iron dependent repressor, metal binding and dimerisation domain
PDB 2hyf EBI.jpg
the structure of apo-mntr from bacillus subtilis, selenomethionine derivative
Identifiers
Symbol Fe_dep_repr_C
Pfam PF02742
Pfam clan CL0123
InterPro IPR001367
SCOP 2dtr
SUPERFAMILY 2dtr

In molecular biology, the iron dependent repressors are a family of bacterial and archaeal transcriptional repressors.

At their N-terminus they contain a dtxR-type HTH domain. This is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 65 amino acids present in metalloregulators of the dtxR/mntR family. The domain is named after Corynebacterium diphtheriae dtxR, an iron-specific diphtheria toxin repressor, and Bacillus subtilis mntR, a manganese transport regulator. Iron-responsive metalloregulators such as dtxR and ideR occur in Gram-positive bacteria of the high GC branch, while manganese-responsive metalloregulators like mntR are described in diverse genera of Gram-positive and Gram-negative bacteria and also in Archaea.[1] The metalloregulators like dtxR/mntR contain the DNA-binding dtxR-type HTHdomain usually in the N-terminal part. The C-terminal part contains a dimerisation domain with two metal-binding sites, although the primary metal-binding site is less conserved in the Mn(II)-regulators. Fe(II)-regulated proteins contain an SH3-like domain as a C-terminal extension, which is absent in Mn(II)-regulated mntR.[2][3]

Metal-ion dependent regulators orchestrate the virulence of several important human pathogens. The dtxR protein regulates the expression of diphtheria toxin in response to environmental iron concentrations. Furthermore, dtxR and ideR control iron uptake.[4] Homeostasis of manganese, which is an essential nutrient, is regulated by mntR. A typical dtxR-type metalloregulator binds two divalent metal effectors per monomer, upon which allosteric changes occur that moderate binding to the cognate DNA operators. Iron-bound dtxR homodimers bind to an interrupted palindrome of 19 bp, protecting a sequence of ~30 bp. The crystal structures of iron-regulated and manganese-regulated repressors show that the DNA binding domain contains three alpha-helices and a pair of antiparallel beta-strands. Helices 2 and 3 comprise the helix-turn-helix motif and the beta-strands are called the wing.[3] This wHTH topology is similar to the lysR-type HTH. Most dtxR-type metalloregulators bind as dimers to the DNA major groove.

Several proteins are known to contain a dtxR-type HTH domain. These include: Corynebacterium diphtheriae dtxR, a diphtheria toxin repressor,[5] which regulates the expression of the high-affinity iron uptake system, other iron-sensitive genes, and the bacteriophage tox gene. Metal-bound dtxR represses transcription by binding the tox operator; if iron is limiting, conformational changes of the wHTH disrupt DNA-binding and the diphtheria toxin is produced. Mycobacterium tuberculosis ideR, an iron-dependent regulator that is essential for this pathogen. The regulator represses genes for iron acquisition and activates iron storage genes, and is a positive regulator of oxidative stress responses.[4] Bacillus subtilis mntR, a manganese transport regulator, binds Mn2+ as an effector and is a transcriptional repressor of transporters for the import of manganese. Treponema pallidum troR, a metal-dependent transcriptional repressor. Archaeoglobus fulgidus MDR1 (troR), a metal-dependent transcriptional repressor, which negatively regulates its own transcription.

References[edit]

  1. ^ Guedon E, Helmann JD (April 2003). "Origins of metal ion selectivity in the DtxR/MntR family of metalloregulators". Mol. Microbiol. 48 (2): 495–506. doi:10.1046/j.1365-2958.2003.03445.x. PMID 12675807. 
  2. ^ Spiering MM, Ringe D, Murphy JR, Marletta MA (April 2003). "Metal stoichiometry and functional studies of the diphtheria toxin repressor". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 3808–13. doi:10.1073/pnas.0737977100. PMC 153003. PMID 12655054. 
  3. ^ a b Glasfeld A, Guedon E, Helmann JD, Brennan RG (August 2003). "Structure of the manganese-bound manganese transport regulator of Bacillus subtilis". Nat. Struct. Biol. 10 (8): 652–7. doi:10.1038/nsb951. PMID 12847518. 
  4. ^ a b Rodriguez GM, Smith I (March 2003). "Mechanisms of iron regulation in mycobacteria: role in physiology and virulence". Mol. Microbiol. 47 (6): 1485–94. doi:10.1046/j.1365-2958.2003.03384.x. PMID 12622807. 
  5. ^ Schiering N, Tao X, Zeng H, Murphy JR, Petsko GA, Ringe D (October 1995). "Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9843–50. doi:10.1073/pnas.92.21.9843. PMC 40899. PMID 7568230. 

This article incorporates text from the public domain Pfam and InterPro IPR022687

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

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Iron dependent repressor, N-terminal DNA binding domain Provide feedback

This family includes the Diphtheria toxin repressor. DNA binding is through a helix-turn-helix motif.

Literature references

  1. Schiering N, Tao X, Zeng H, Murphy JR, Petsko GA, Ringe D; , Proc Natl Acad Sci USA 1995;92:9843-9850.: Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae. PUBMED:7568230 EPMC:7568230

  2. Qiu X, Verlinde CL, Zhang S, Schmitt MP, Holmes RK, Hol WG; , Structure 1995;3:87-100.: Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors. PUBMED:7743135 EPMC:7743135


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022687

The DtxR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 65 residues present in metalloregulators of the DtxR/MntR family. The family is named after Corynebacterium diphtheriae DtxR, an iron-specific diphtheria toxin repressor, and Bacillus subtilis MntR, a manganese transport regulator. Iron-responsive metalloregulators such as DtxR and IdeR occur in Gram-positive bacteria of the high GC branch, while manganese-responsive metalloregulators like MntR are described in diverse genera of Gram-positive and Gram-negative bacteria and also in Archaea [PUBMED:12675807].The metalloregulators like DtxR/MntR contain the DNA-binding DtxR-type HTH domain usually in the N-terminal part. The C-terminal part contains a dimerisation domain with two metal-binding sites, although the primary metal-binding site is less conserved in the Mn(II)-regulators. Fe(II)-regulated proteins contain an SH3-like domain as a C-terminal extension, which is absent in Mn(II)-regulated MntR [PUBMED:12655054, PUBMED:12847518].

Metal-ion dependent regulators orchestrate the virulence of several important human pathogens. The DtxR protein regulates the expression of diphtheria toxinin response to environmental iron concentrations. Furthermore, DtxR and IdeR control iron uptake [PUBMED:12622807]. Homeostasis of manganese, which is an essential nutrient, is regulated by MntR. A typical DtxR-type metalloregulator binds two divalent metal effectors per monomer, upon which allosteric changes occur that moderate binding to the cognate DNA operators. Iron-bound DtxR homodimers bind to an interrupted palindrome of 19 bp, protecting a sequence of ~30 bp. The crystal structures of iron-regulated and manganese-regulated repressors show that the DNA binding domain contains three alpha-helices and a pair of antiparallel beta-strands. Helices 2 and 3 comprise the helix-turn-helix motif and the beta-strands are called the wing [PUBMED:12847518]. This wHTH topology is similar to the lysR-type HTH (see PROSITEDOC). Most DtxR-type metalloregulators bind as dimers to the DNA major groove.

Several proteins are known to contain a DtxR-type HTH domain. These include- Corynebacterium diphtheriae DtxR, a diphtheria toxin repressor [PUBMED:7568230], which regulates the expression of the high-affinity iron uptake system, other iron-sensitive genes, and the bacteriophage tox gene. Metal-bound DtxR represses transcription by binding the tox operator; if iron is limiting, conformational changes of the wHTH disrupt DNA-binding and the diphtheria toxin is produced. Mycobacterium tuberculosis IdeR, an iron-dependent regulator that is essential for this pathogen. The regulator represses genes for iron acquisition and activates iron storage genes, and is a positive regulator of oxidative stress responses [PUBMED:12622807]. Bacillus subtilis MntR, a manganese transport regulator, binds Mn2+ as an effector and is a transcriptional repressor of transporters for the import of manganese. Treponema pallidum troR, a metal-dependent transcriptional repressor. Archaeoglobus fulgidus MDR1 (troR), a metal-dependent transcriptional repressor, which negatively regulates its own transcription.

This entry covers the entire DtxR-type HTH domain.

Gene Ontology

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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 202 members:

AphA_like 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 DUF2250 DUF2316 DUF3116 DUF3853 DUF387 DUF3908 DUF4095 DUF4364 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 HARE-HTH 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_40 HTH_41 HTH_42 HTH_43 HTH_45 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_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 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 P22_Cro PaaX PadR PAX PCI PCI_Csn8 Penicillinase_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

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Full
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Representative proteomes NCBI
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Meta
(836)
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RP35
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RP55
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  Seed
(10)
Full
(3362)
Representative proteomes NCBI
(4553)
Meta
(836)
RP15
(286)
RP35
(561)
RP55
(700)
RP75
(779)
Alignment:
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  Seed
(10)
Full
(3362)
Representative proteomes NCBI
(4553)
Meta
(836)
RP15
(286)
RP35
(561)
RP55
(700)
RP75
(779)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Pfam alignments:

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Trees

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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: Sarah Teichmann
Previous IDs: none
Type: Domain
Author: Bateman A, Griffiths-Jones SR
Number in seed: 10
Number in full: 3362
Average length of the domain: 59.00 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 32.07 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.6 21.6
Trusted cut-off 21.6 21.6
Noise cut-off 21.5 21.5
Model length: 60
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 3 interactions for this family. More...

FeoA Fe_dep_repress Fe_dep_repr_C

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 Fe_dep_repress domain has been found. There are 94 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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