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Arsenical pump membrane protein
Arsenical pump membrane protein
Identifiers
Symbol	ArsB
Pfam	PF02040
InterPro	IPR000802
TCDB	2.A.45
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	IF48

Arsenite and Antimonite Efflux Pump
Arsenite and Antimonite Efflux Pump
Identifiers
Symbol	ArsA
Pfam	PF02374
InterPro	IPR027541
SMART	SM00382
TCDB	3.A.4
OPM superfamily	124
OPM protein	3sja
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	IF48

Arsenite resistance (Ars) efflux pumps of bacteria may consist of two proteins, ArsB (TC# 2.A.45.1.1; the integral membrane constituent with twelve transmembrane spanners) and ArsA (TC# 3.A.4.1.1; the ATP-hydrolyzing, transport energizing subunit, as for the chromosomally-encoded E. coli system), or of one protein (just the ArsB integral membrane protein of the plasmid-encoded Staphylococcus system).^[1]^[2]^[3] 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 (i.e.,TC# 2.A.45). When ArsA is also present, ATP hydrolysis drives efflux, and consequently the system belongs in TC subclass 3.A (i.e., TC# 3.A.4). ArsB therefore appears twice in the TC system (ArsB and ArsAB) but ArsA appears only once. These pumps actively expel both arsenite and antimonite.^[1]^[2]^[3]^[4]

Homology

Homologues of ArsB are found in Gram-negative and Gram-positive bacteria as well as cyanobacteria. Homologues are also found in archaea and eukarya. Several paralogues may sometimes be found in a single organism. Among the distant homologues found in eukaryotes are members of the DASS family (TC# 2.A.47) including the rat renal Na⁺:sulfate cotransporter (Q07782) and the human renal Na⁺:dicarboxylate cotransporter (gbU26209^{[permanent dead link‍]}). ArsB proteins are therefore members of a superfamily (called the IT (ion transporter) superfamily).^[5]^[6] However, ArsB has uniquely gained the ability to function in conjunction with ArsA in order to couple ATP hydrolysis to anion efflux. ArsAB belongs to the ArsA ATPase Superfamily.

Debatably, a unique member of the ArsB family is the rice silicon (silicate) efflux pump, Lsi2 (TC# 2.A.45.2.4). The silicon uptake systems, Lsi1 (TC# 1.A.8.12.2), and Lsi2 are expressed in roots, on the plasma membranes of cells in both the exodermis and the endodermis. In contrast to Lsi1, which is localized on the distal side, Lsi2 is localized on the proximal side of the same cells. Thus these cells have an influx transporter on one side and an efflux transporter on the other side of the cell to permit the effective transcellular transport of the nutrient.^[7]^[8]

ArsA proteins are homologous to nitrogenase iron (NifH) proteins 2 of bacteria and to protochlorophyllide reductase iron sulfur ATP-binding proteins of cyanobacteria, algae and plants.

Mechanism

ArsA homologues are found in bacteria, archaea and eukarya (both animals and plants), but there are far fewer of them in the databases than ArsB proteins, suggesting that many ArsB homologues function by a pmf-dependent mechanism, probably an arsenite:H⁺ antiport mechanism.^[9]

In the E. coli ArsAB transporter, both ArsA and ArsB recognize and bind their anionic substrates. A model has been proposed in which ArsA alternates between two virtually exclusive conformations.^[10] In one, (ArsA¹) the A1 site is closed but the A2 site is open, but in the other (ArsA²) the opposite is true. Antimonite [Sb(III)] sequesters ArsA in the ArsA¹ conformation which catalyzes ATP hydrolysis at A2 to drive ArsA between conformations that have high (nucleotide-bound ArsA) and low (nucleotide-free ArsA) affinity for antimonite. It is proposed that ArsA uses this process to sequester Sb(III) and eject it into the ArsB channel.^[10]^[9]^[11]

In the case of ArsAB, at the interface of these two halves are two nucleotide-binding domains and a metalloid-binding domain.^[12] Cys-113 and Cys-422 have been shown to form a high-affinity metalloid binding site. The crystal structure of ArsA shows two other bound metalloid atoms, one liganded to Cys-172 and His-453, and the other liganded to His-148 and Ser-420. There is only a single high-affinity metalloid binding site in ArsA. Cys-172 controls the affinity of this site for metalloid and hence the efficiency of metalloactivation of the ArsAB efflux pump.^[12]