ARC3 family

Last updated

The arsenical resistance-3 (ACR3) family (TC# 2.A.59) is a member of the BART superfamily. [1] Based on operon analyses, ARC3 homologues may function either as secondary carriers or as primary active transporters, similarly to the ArsB and ArsAB families. In the latter case ATP hydrolysis again energizes transport. ARC3 homologues transport the same anions as ArsA/AB homologues, though ArsB homologues are members of the IT Superfamily and homologues of the ARC3 family are within the BART Superfamily suggesting they may not be evolutionarily related.

Contents

Structure and Homology

Bacillus ARC3 (ArsB; TC# 2.A.59.1.2) probably has a 10 TMS topology. [2] ACR3 of S. cerevisiae is 404 amino acyl residues long and exhibits 10 putative transmembrane α-helical spanners (TMSs). Homologues are found in Mycobacterium tuberculosis (498 aas; gbZ80225), Archaeoglobus fulgidus (370 aas; gbAE001071), Methanobacterium thermoautotrophicum (365 aas; gbAE000865) and Synechocystis (383 aas; spP74311). Thus, members of the ACR3 family are found in bacteria, archaea and eukarya. Sequence similarity of several members of the ACR3 family with members of the bile acid:Na+ symporter (BASS) family (TC# 2.A.28) is sufficient to establish homology.

Bioinformatic analyses have revealed that some ACR3 porters are involved in operons together with ArsA-like ATPases, implying that some of these porters may be driven by ATP hydrolysis as primary active transporters. [3] This may occur in addition to or instead of the secondary active transport mechanism established for ACR3 members noted above. Homologous ATPases are found in families TC# 3.A.4, TC# 3.A.19 and TC# 3.A.21 as well as TC# 2.A.59. A region of the ABC ATPase (TC# 3.A.1.26.8; the ribose transporter) shows significant sequence similarity to the ArsA under TC# 3.A.19.1.1 (28% identical; 49% similarity, 0 gaps, e−5) as revealed by TC Blast. [3] [4]

Function

Two proteins of the ACR3 family have been functionally characterized. These proteins are the ACR3 protein of Saccharomyces cerevisiae, also called the ARR3 protein, [5] and the 'ArsB' protein of Bacillus subtilis. [6] While the nomenclature of the ARC3 ArsB protein overlaps with ArsB of E. coli (ArsB family), it is important to note they are not related. The former yeast protein is present in the plasma membrane and pumps arsenite and antimonite, but not arsenate, tellurite, cadmium or phenylarsine oxide out of the cell in response to the proton motive force (pmf). It uses a proton antiport mechanism to extrude the anions with low affinity. [7] The Bacillus protein exports both arsenite and antimonite. The exact transport mechanism has not established.

The generalized reaction catalyzed by members of the ACR3 family is: [4]

arsenite or antimonite (in) → arsenite or antimonite (out).

See also

Further reading

Related Research Articles

The Nucleobase:Cation Symporter-1 (NCS1) Family (TC# 2.A.39) consists of over 1000 currently sequenced proteins derived from Gram-negative and Gram-positive bacteria, archaea, fungi and plants. These proteins function as transporters for nucleobases including purines and pyrimidines. Members of this family possess twelve transmembrane α-helical spanners (TMSs). At least some of them have been shown to function in uptake by substrate:H+ symport mechanism.

Ars operon

In molecular biology, the ars operon is an operon found in several bacterial taxon. It is required for the detoxification of arsenate, arsenite, and antimonite. This system transports arsenite and antimonite out of the cell. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. Arsenate, however, must first be reduced to arsenite before it is extruded. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC is an approximately 150-residue arsenate reductase that uses reduced glutathione (GSH) to convert arsenate to arsenite with a redox active cysteine residue in the active site. ArsC forms an active quaternary complex with GSH, arsenate, and glutaredoxin 1 (Grx1). The three ligands must be present simultaneously for reduction to occur.

The Nucleobase cation symporter-2 (NCS2) family, also called the Nucleobase ascorbate transporter (NAT) family, consists of over 1000 sequenced proteins derived from gram-negative and gram-positive bacteria, archaea, fungi, plants and animals. The NCS2/NAT family is a member of the APC Superfamily of secondary carriers. Of the five known families of transporters that act on nucleobases, NCS2/NAT is the only one that is most widespread. Many functionally characterized members are specific for nucleobases including both purines and pyrimidines, but others are purine-specific. However, two closely related rat/human members of the family, SVCT1 and SVCT2, localized to different tissues of the body, co-transport L-ascorbate (vitamin C) and Na+ with a high degree of specificity and high affinity for the vitamin. Clustering of NCS2/NAT family members on the phylogenetic tree is complex, with bacterial proteins and eukaryotic proteins each falling into at least three distinct clusters. The plant and animal proteins cluster loosely together, but the fungal proteins branch from one of the three bacterial clusters forming a tighter grouping. E. coli possesses four distantly related paralogous members of the NCS2 family.

Mercury transporter

The mercury transporter superfamily is a family of transmembrane bacterial transporters of mercury ions. The common origin of all Mer superfamily members has been established. The common elements between family members are included in TMSs 1-2. A representative list of the subfamilies and proteins that belong to those subfamilies is available in the Transporter Classification Database.

The Amino Acid-Polyamine-Organocation (APC) Family of transport proteins includes members that function as solute:cation symporters and solute:solute antiporters. They occur in bacteria, archaea, fungi, unicellular eukaryotic protists, slime molds, plants and animals. They vary in length, being as small as 350 residues and as large as 850 residues. The smaller proteins are generally of prokaryotic origin while the larger ones are of eukaryotic origin. Most of them possess twelve transmembrane α-helical spanners but have a re-entrant loop involving TMSs 2 and 3. The APC Superfamily was established to encompass a wider range of homologues.

The sulfate permease (SulP) family is a member of the large APC superfamily of secondary carriers. The SulP family is a large and ubiquitous family of proteins derived from archaea, bacteria, fungi, plants and animals. Many organisms including Bacillus subtilis, Synechocystis sp, Saccharomyces cerevisiae, Arabidopsis thaliana and Caenorhabditis elegans possess multiple SulP family paralogues. Many of these proteins are functionally characterized, and most are inorganic anion uptake transporters or anion:anion exchange transporters. Some transport their substrate(s) with high affinities, while others transport it or them with relatively low affinities. Others may catalyze SO2−
4:HCO−
3 exchange, or more generally, anion:anion antiport. For example, the mouse homologue, SLC26A6, can transport sulfate, formate, oxalate, chloride and bicarbonate, exchanging any one of these anions for another. A cyanobacterial homologue can transport nitrate. Some members can function as channels. SLC26A3 and SLC26A6 can function as carriers or channels, depending on the transported anion. In these porters, mutating a glutamate, also involved in transport in the CIC family, created a channel out of the carrier. It also changed the stoichiometry from 2Cl−/HCO−
3 to 1Cl−/HCO−
3.

The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) flippase superfamily is a group of integral membrane protein families. The MOP flippase superfamily includes twelve distantly related families, six for which functional data are available:

  1. One ubiquitous family (MATE) specific for drugs - (TC# 2.A.66.1) The Multi Antimicrobial Extrusion (MATE) Family
  2. One (PST) specific for polysaccharides and/or their lipid-linked precursors in prokaryotes - (TC# 2.A.66.2) The Polysaccharide Transport (PST) Family
  3. One (OLF) specific for lipid-linked oligosaccharide precursors of glycoproteins in eukaryotes - (TC# 2.A.66.3) The Oligosaccharidyl-lipid Flippase (OLF) Family
  4. One (MVF) lipid-peptidoglycan precursor flippase involved in cell wall biosynthesis - (TC# 2.A.66.4) The Mouse Virulence Factor (MVF) Family
  5. One (AgnG) which includes a single functionally characterized member that extrudes the antibiotic, Agrocin 84 - (TC# 2.A.66.5) The Agrocin 84 Antibiotic Exporter (AgnG) Family
  6. And finally, one (Ank) that shuttles inorganic pyrophosphate (PPi) - (TC# 2.A.66.9) The Progressive Ankylosis (Ank) Family

The iron/lead transporter (ILT) family is a family of transmembrane proteins within the lysine exporter (LysE) superfamily. The ILT family includes two subfamilies, the iron-transporting (OFeT) family and the lead-transporting (PbrT) family. A representative list of the proteins belonging to these subfamilies of the ILT family can be found in the Transporter Classification Database.

The gluconate:H+ symporter (GntP) family (TC# 2.A.8) is a family of transport proteins belonging to the ion transporter (IT) superfamily. Members of the GntP family include known gluconate permeases of E. coli and Bacillus species such as the D-Gluconate:H+ symporter of Bacillus subtillus (GntP; TC# 2.A.8.1.1) and the D-fructuronate/D-gluconate:H+ symporter of E. coli (GntP; TC# 2.A.8.1.3). A representative list of proteins belonging to the GntP family can be found in the Transporter Classification Database.

Arsenite-antimonite transporters are membrane transporters that pump arsenite or antimonite out of a cell. Antimonite is the salt of antimony and has been found to significantly impact the toxicity of arsenite. The similar structure of As(III) and Sb(III) makes it plausible that certain transporters function in the efflux of both substrates. Arsenic efflux transporters exist in almost every organism and serve to remove this toxic compound from the cell.

Divalent anion:Na+ symporters were found in bacteria, archaea, plant chloroplasts and animals.

The ion transporter (IT) superfamily is a superfamily of secondary carriers that transport charged substrates.

The Citrate-Mg2+:H+ (CitM) / Citrate-Ca2+:H+ (CitH) Symporter (CitMHS) Family (TC# 2.A.11) is a family of transport proteins belonging to the Ion transporter superfamily. Members of this family are found in Gram-positive and Gram-negative bacteria, archaea and possibly eukaryotes. These proteins all probably arose by an internal gene duplication event. Lensbouer & Doyle (2010) have reviewed these systems, classifying the porters with three superfamilies, according to ion-preference:

Arsenite resistance (Ars) efflux pumps of bacteria may consist of two proteins, ArsB and ArsA, or of one protein. ArsA proteins have two ATP binding domains and probably arose by a tandem gene duplication event. ArsB proteins all possess twelve transmembrane spanners and may also have arisen by a tandem gene duplication event. Structurally, the Ars pumps resemble ABC-type efflux pumps, but there is no significant sequence similarity between the Ars and ABC pumps. When only ArsB is present, the system operates by a pmf-dependent mechanism, and consequently belongs in TC subclass 2.A. When ArsA is also present, ATP hydrolysis drives efflux, and consequently the system belongs in TC subclass 3.A. ArsB therefore appears twice in the TC system but ArsA appears only once. These pumps actively expel both arsenite and antimonite.

The 6TMS Neutral Amino Acid Transporter (NAAT) Family is a family of transporters belonging to the Lysine Exporter (LysE) Superfamily. Homologues are found in numerous Gram-negative and Gram-positive bacteria including many human pathogens. Several archaea also encode MarC homologues. Some of these organisms have 2 or more paralogues. Most of these proteins are of about the same size although a few are larger. They exhibit 6 putative TMSs. A representative list of members belonging to the NAAT family can be found in the Transporter Classification Database.

The Basic Amino Acid Antiporter (ArcD) family is a constituent of the IT superfamily. This family consists of proteins from Gram-negative and Gram-positive bacteria. The proteins are of about 480 amino acyl residues (aas) in length and have 10-12 putative transmembrane segments (TMSs). Functionally characterized homologues are in the DcuC and ArsB families. Some members of the family probably catalyze arginine/ornithine or citrulline/ornithine antiport.

The NhaC family belongs to the Ion Transporter (IT) Superfamily. A representative list of proteins belonging to the NhaC family can be found in the Transporter Classification Database.

The Monovalent Cation (K+ or Na+):Proton Antiporter-3 (CPA3) Family (TC# 2.A.63) is a member of the Na+ transporting Mrp superfamily. The CPA3 family consists of bacterial multicomponent K+:H+ and Na+:H+ antiporters. The best characterized systems are the PhaABCDEFG system of Sinorhizobium meliloti (TC# 2.A.63.1.1) that functions in pH adaptation and as a K+ efflux system, and the MnhABCDEFG system of Staphylococcus aureus (TC# 2.A.63.1.3) that functions as a Na+ efflux Na+:H+ antiporter.

The inorganic phosphate transporter (PiT) family is a group of carrier proteins derived from Gram-negative and Gram-positive bacteria, archaea, and eukaryotes.

The Holin superfamily IV is a superfamily of integral membrane transport proteins. It is one of the seven different holin superfamilies in total.

References

  1. ↑ Mansour, Nahla M.; Sawhney, Mrinalini; Tamang, Dorjee G.; Vogl, Christian; Saier, Milton H. (2007-02-01). "The bile/arsenite/riboflavin transporter (BART) superfamily". The FEBS Journal. 274 (3): 612–629. doi: 10.1111/j.1742-4658.2006.05627.x . PMID   17288550. S2CID   12444163.
  2. ↑ Aaltonen, Emil K. J.; Silow, Maria (2008-04-01). "Transmembrane topology of the Acr3 family arsenite transporter from Bacillus subtilis". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1778 (4): 963–973. doi: 10.1016/j.bbamem.2007.11.011 . PMID   18088595.
  3. 1 2 Castillo, Rostislav; Saier, Milton H. (2010-01-01). "Functional Promiscuity of Homologues of the Bacterial ArsA ATPases". International Journal of Microbiology. 2010: 187373. doi: 10.1155/2010/187373 . PMC   2963123 . PMID   20981284.
  4. 1 2 "2.A.59 The Arsenical Resistance-3 (ACR3) Family". Transporter Classification Database. Retrieved 2016-03-13.
  5. ↑ Wysocki, R.; Bobrowicz, P.; Ułaszewski, S. (1997-11-28). "The Saccharomyces cerevisiae ACR3 gene encodes a putative membrane protein involved in arsenite transport". The Journal of Biological Chemistry. 272 (48): 30061–30066. doi: 10.1074/jbc.272.48.30061 . PMID   9374482.
  6. ↑ Sato, T.; Kobayashi, Y. (1998-04-01). "The ars operon in the skin element of Bacillus subtilis confers resistance to arsenate and arsenite". Journal of Bacteriology. 180 (7): 1655–1661. doi:10.1128/JB.180.7.1655-1661.1998. PMC   107075 . PMID   9537360.
  7. ↑ Maciaszczyk-Dziubinska, Ewa; Migocka, Magdalena; Wysocki, Robert (2011-07-01). "Acr3p is a plasma membrane antiporter that catalyzes As(III)/H(+) and Sb(III)/H(+) exchange in Saccharomyces cerevisiae". Biochimica et Biophysica Acta. 1808 (7): 1855–1859. doi: 10.1016/j.bbamem.2011.03.014 . PMID   21447319.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.