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0  structures 3512  species 0  interactions 25983  sequences 35  architectures

Family: DctM (PF06808)

Summary: Tripartite ATP-independent periplasmic transporter, DctM component

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This is the Wikipedia entry entitled "Tripartite ATP-independent periplasmic transporter". More...

Tripartite ATP-independent periplasmic transporter Edit Wikipedia article

DctP component of Tripartite ATP-independent periplasmic transporter
Identifiers
SymbolDctP
PfamPF03480
Pfam clanCL0177
InterProIPR018389
TCDB2.A.56
DctQ component of Tripartite ATP-independent periplasmic transporter
Identifiers
SymbolDctQ
PfamPF04290
InterProIPR007387
TCDB2.A.56
DctM-like transporters
Identifiers
SymbolDctM
PfamPF06808
Pfam clanCL0182
InterProIPR010656
TCDB2.A.56

Tripartite ATP-independent periplasmic transporters (TRAP transporters) are a large family of solute transporters found in bacteria and archaea, but not in eukaryotes, that appear to be specific for the uptake of organic acids or related molecules containing a carboxylate or sulfonate group. They are unique in that they utilize a substrate binding protein (SBP) in combination with a secondary transporter.

History

A schematic illustrating the key features of a TRAP transporter in comparison to an ABC transporter and a classical secondary transporter.

TRAP transporters were discovered in the laboratory of Prof. David J. Kelly at the University of Sheffield, UK. His group were working on the mechanism used by the photosynthetic bacterium Rhodobacter capsulatus to take up certain dicarboxylic acids. They characterised a binding protein component (DctP) of a transporter that recognized these compounds, which they assumed would form part of a typical ABC transporter, but when they sequenced the genes surrounding dctP they found two other genes encoding integral membrane proteins, dctQ and dctM, but no genes encoding components of an ABC transporter.[1] They further showed that uptake of the same dicarboxylates was independent of ATP and that uptake required an electrochemical ion gradient, making this a unique binding protein-dependent secondary transporter.[1]

Since these early studies, it has become clear that TRAP transporters are present in many bacteria and archaea,[2] with many bacterial having multiple TRAP transporters, some having over 20 different systems.[3]

Substrates

To date, most substrates for TRAP transporters contain a common feature which is that they are organic acids.[4] This includes C4-dicarboxylates such as succinate, malate and fumarate,[1] keto-acids such as pyruvate and alpha-ketobutyrate[5][6] and the sugar acid, N-acetyl neuraminic acid (or sialic acid).[7] Other substrates include the compatible solute ectoine and hydroxyectoine and pyroglutamate.[4]

Composition

All known TRAP transporters contain 3 protein domains. These are the solute binding protein (the SBP), the small membrane protein domain and the large membrane protein domain. Following the nomenclature for the first characterized TRAP transporter, DctPQM, these subunits are usually named P, Q and M respectively.[4] Around 10% of TRAP transporters have natural genetic fusions between the two membrane protein components, and in the one well studied example of this in the sialic acid specific TRAP transporter from Haemophilus influenzae the fused gene has been named siaQM. The large M subunit is predicted to have 12 transmembrane helices and the small Q subunit to have 4 transmembrane helices and the fused QM proteins are predicted to have 17 transmembrane helices.[4]

Mechanism

By using an SBP, TRAP transporters share some similarity to ABC transporters in that the substrate for the transporter is initially recognized outside of the cytoplasmic membrane. In Gram-negative bacteria, the SBP is usually free in the periplasm and expressed at relatively high levels compared to the membrane domains.[1] In Gram positive bacteria and archaea, the SBP is tethered to the cytoplasmic membrane. In both types of systems the SBP binds to substrate, usually with low micromolar affinity,[4] which causes a significant conformation change in the protein, akin to a Venus flytrap closing. The trapped subtrate is then delivered to the membrane domains of the transporter, where the electrochemical ion gradient is somehow exploited to open the SBP, extract the substrate and catalyse its movement across the membrane. For the SiaPQM TRAP transporter which has been studied in a fully reconstituted in vitro form, uptake uses a Na+
 gradient and not proton gradient to drive uptake.[8] The SiaPQM systems also exhibits unique properties for a secondary transporter in that it cannot catalyse bidirectional transport as the SBP imposes that movement is only in the direction of uptake into the cell.[8]

Structure

Substrate binding protein (SBP)

Following the first structure of a TRAP SBP in 2005,[9] there are now over 10 different structures available.[10][11][12] They all have very similar overall structures, with two globular domains linked by a hinge. The substrate binding site is formed by both the domains which enclose the substrate. A highly conserved arginine residue in the TRAP SBPs forms a salt bridge with a carboxylate group on the substrate, which is important for substrate recognition.[10]

Membrane subunits

There are currently no structures for the membrane domains of any TRAP transporter. It is not even known which subunit(s) made a direct interaction with the SBP subunit during the transport cycle.

References

  1. ^ a b c d Forward J.A.; Behrendt M.C.; Wyborn N.R.; Cross R.; Kelly D.J. (1997). "TRAP transporters: a new family of periplasmic solute transport systems encoded by the dctPQM genes of Rhodobacter capsulatus and by homologs in diverse gram-negative bacteria". J. Bacteriol. 179 (17): 5482–5493. PMC 179420. PMID 9287004.
  2. ^ Rabus R.; Jack D.L.; Kelly D.J.; Saier M.H. Jr. (1999). "TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters". Microbiology. 145 (12): 3431–3445. doi:10.1099/00221287-145-12-3431. PMID 10627041.
  3. ^ Mulligan C.; Kelly D.J.; Thomas G.H. (2007). "Tripartite ATP-independent periplasmic transporters: application of a relational database for genome-wide analysis of transporter gene frequency and organization". J. Mol. Microbiol. Biotechnol. 12 (3–4): 218–226. doi:10.1159/000099643. PMID 17587870.
  4. ^ a b c d e Mulligan C.; Fischer M.; Thomas G. (2010). "Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea". FEMS Microbiol. Rev. 35 (1): 68–86. doi:10.1111/j.1574-6976.2010.00236.x. PMID 20584082.
  5. ^ Thomas GH, Southworth T, León-Kempis MR, Leech A, Kelly DJ (2006). "Novel ligands for the extracellular solute receptors of two bacterial TRAP transporters". Microbiology. 152 (2): 187–198. doi:10.1099/mic.0.28334-0. PMID 16385129.
  6. ^ Pernil R, Herrero A, Flores E (2010). "A TRAP transporter for pyruvate and other monocarboxylate 2-oxoacids in the cyanobacterium Anabaena sp. strain PCC 7120". J. Bacteriol. 192 (22): 6089–6092. doi:10.1128/JB.00982-10. PMC 2976462. PMID 20851902.
  7. ^ Severi E, Randle G, Kivlin P, Whitfield K, Young R, Moxon R, Kelly D, Hood D, Thomas GH (2005). "Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter". Mol. Microbiol. 58 (4): 1173–1185. doi:10.1111/j.1365-2958.2005.04901.x. PMID 16262798.
  8. ^ a b Mulligan C.; Geertsma E.R.; Severi E.; Kelly D.J.; Poolman B.; Thomas G.H. (2009). "The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter". Proc. Natl. Acad. Sci. USA. 106 (6): 1778–1783. doi:10.1073/pnas.0809979106. PMC 2644114. PMID 19179287.
  9. ^ Müller A.; Severi E.; Mulligan C.; Watts A.G.; Kelly D.J.; Wilson K.S.; Wilkinson A.J.; Thomas G.H. (2006). "Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae" (PDF). J. Biol. Chem. 281 (31): 22212–22222. doi:10.1074/jbc.M603463200. PMID 16702222.
  10. ^ a b Johnston J.W.; Coussens N.P.; Allen S.; Houtman J.C.; Turner K.H.; Zaleski A.; Ramaswamy S.; Gibson B.W.; Apicella M.A. (2008). "Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019". J. Biol. Chem. 283 (2): 855–865. doi:10.1074/jbc.M706603200. PMID 17947229.
  11. ^ Gonin S.; Arnoux P.; Pierru B.; Lavergne J.; Alonso B.; Sabaty M.; Pignol D. (2007). "Crystal structures of an Extracytoplasmic Solute Receptor from a TRAP transporter in its open and closed forms reveal a helix-swapped dimer requiring a cation for alpha-keto acid binding". BMC Struct. Biol. 7: 11. doi:10.1186/1472-6807-7-11. PMC 1839085. PMID 17362499.
  12. ^ Fischer M, Zhang QY, Hubbard RE, Thomas GH (2010). "Caught in a TRAP: substrate-binding proteins in secondary transport". Trends Microbiol. 18 (10): 471–478. doi:10.1016/j.tim.2010.06.009. PMID 20656493.

External links

  • [1] The lab page of Prof. David Kelly, University of Sheffield, UK
  • [2] The lab page of Dr. Gavin Thomas, University of York, UK.

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Tripartite ATP-independent periplasmic transporter, DctM component Provide feedback

This family contains a diverse range of predicted transporter proteins. Including the DctM subunit of the bacterial and archaeal TRAP C4-dicarboxylate transport (Dct) system permease. In general, C4-dicarboxylate transport systems allow C4-dicarboxylates like succinate, fumarate, and malate to be taken up. TRAP C4-dicarboxylate carriers are secondary carriers that use an electrochemical H+ gradient as the driving force for transport. DctM is an integral membrane protein that is one of the constituents of TRAP carriers [1]. Note that many family members are hypothetical proteins.

Literature references

  1. Janausch IG, Zientz E, Tran QH, Kroger A, Unden G; , Biochim Biophys Acta 2002;1553:39-56.: C4-dicarboxylate carriers and sensors in bacteria. PUBMED:11803016 EPMC:11803016

Internal database links

SCOOP: ArsB CitMHS DcuC GntP_permease Lactate_perm MatC_N Na_H_antiport_2 Na_H_antiporter Na_sulph_symp TrkA_C
Similarity to PfamA using HHSearch: GntP_permease CitMHS DcuC

External database links

Transporter classification: 2.A.56

This tab holds annotation information from the InterPro database.

InterPro entry IPR010656

This domain represents a conserved region located towards the N terminus of the DctM subunit of the bacterial and archaeal TRAP C4-dicarboxylate transport (Dct) system permease. In general, C4-dicarboxylate transport systems allow C4-dicarboxylates like succinate, fumarate, and malate to be taken up. TRAP C4-dicarboxylate carriers are secondary carriers that use an electrochemical H + gradient as the driving force for transport. DctM is an integral membrane protein that is one of the constituents of TRAP carriers [ PUBMED:11803016 , PUBMED:11524131 ]. Note that many family members are hypothetical proteins.

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 IT (CL0182), which has the following description:

This superfamily of secondary carriers specific for cationic and anionic compounds, has been termed the ion transporter (IT) superfamily [1].

The clan contains the following 22 members:

ABG_transport ArsB ArsP_1 ArsP_2 CitMHS CitMHS_2 DctM DcuA_DcuB DcuC DUF1646 DUF401 EutH EXS GntP_permease Lactate_perm MatC_N Na_H_antiport_2 Na_H_antiport_3 Na_H_antiporter Na_sulph_symp NhaB SCFA_trans

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 and the UniProtKB sequence database. More...

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  Seed
(17)		 Full
(25983)		 Representative proteomes UniProt
(101780)
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(2759)		 RP35
(12895)		 RP55
(26984)		 RP75
(43469)
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  Seed
(17)		 Full
(25983)		 Representative proteomes UniProt
(101780)
RP15
(2759)		 RP35
(12895)		 RP55
(26984)		 RP75
(43469)
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  Seed
(17)		 Full
(25983)		 Representative proteomes UniProt
(101780)
RP15
(2759)		 RP35
(12895)		 RP55
(26984)		 RP75
(43469)
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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.

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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: Pfam-B_4075 (release 10.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Vella Briffa B , Bateman A
Number in seed: 17
Number in full: 25983
Average length of the domain: 403.30 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 86.14 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.8 23.8
Trusted cut-off 23.8 23.8
Noise cut-off 23.7 23.7
Model length: 416
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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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
P37675 View 3D Structure Click here
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trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.

Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;