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Review
. 2019 May;126:585-597.
doi: 10.1016/j.envint.2019.02.058. Epub 2019 Mar 8.

Pathways of Arsenic Uptake and Efflux

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Free PMC article
Review

Pathways of Arsenic Uptake and Efflux

Luis D Garbinski et al. Environ Int. .
Free PMC article

Abstract

Arsenic is a non-essential, environmentally ubiquitous toxic metalloid. In response to this pervasive environmental challenge, organisms evolved mechanisms to confer resistance to arsenicals. Inorganic pentavalent arsenate is taken into most cells adventitiously by phosphate uptake systems. Similarly, inorganic trivalent arsenite is taken into most cells adventitiously, primarily via aquaglyceroporins or sugar permeases. The most common strategy for tolerance to both inorganic and organic arsenicals is by efflux that extrude them from the cytosol. These efflux transporters span across kingdoms and belong to various families such as aquaglyceroporins, major facilitator superfamily (MFS) transporters, ATP-binding cassette (ABC) transporters and potentially novel, yet to be discovered families. This review will outline the properties and substrates of known arsenic transport systems, the current knowledge gaps in the field, and aims to provide insight into the importance of arsenic transport in the context of the global arsenic biogeocycle and human health.

Keywords: Arsenate; Arsenic permeases; Arsenic resistance; Arsenite; Methylarsenite.

Conflict of interest statement

Declarations of interest: none.

Figures

Figure 1.
Figure 1.. Structure of As(III) uptake proteins GlpF and GLUT1.
GlpF (PDB accession code 1FX8) and GLUT1 (PDB accession code 4PYP) facilitate As(III) entry into cells. Left: Aquaglyceroporins such as GlpF have six transmembrane ɑ-helices and two half-helices. The two half-helices align to span the membrane. Each half helix has an NPA motifs (orange) that form a constriction that contributes to exclusion of protons and gives selectivity for uncharged substrates. Right: MFS sugar permeases such as GLUT1 have two six-helix halves that fold together to form a central cavity into which substrate binds. In the cytosol substrate binds to the cavity in an inward-facing conformation. A conformational change reorients binding site to an outward-facing conformation, with release of substrate from the cell.
Figure 2.
Figure 2.. ArsB, Acr3, ArsP phylogenic trees.
A neighbor-joining phylogenetic tree showing the divergent from three arsenic efflux proteins: ArsB, Acr3, and ArsP. To obtain sequences of arsP genes encoding candidate orthologs, ArsP (Campylobacter jejuni RM1221), ACG76368, was used for Basic Local Alignment Search Tool (BLAST). Only sequences containing a highly conserved MAs(III) binding motif (TPFCSCSXXP) were included. To obtain sequences of arsB genes encoding candidate orthologs, ArsB (Escherichia coli), AJE59278, was used for BLAST. To obtain sequences of acr3 genes encoding candidate orthologs, Acr3 (Corynebacterium glutamicum), BAV22061, was used for blast. The tree was produced using MEGA7. Bacterial species and protein accession numbers are shown.
Figure 3.
Figure 3.. Transmembrane topology of arsenic permeases.
While the number of predicted TMs for ArsB and ArsK (A) supports their classification as MFS transporters, other pumps such as Acr3 (A), ArsJ, and ArsP (B) are predicted to have fewer than 12 TMs. The ArsB and Acr3 topologies are based on experimental data. ArsJ, ArsP and ArsK topologies are predicted from in silico analysis. Transmembrane topology models were calculated with TMHMM and illustrated with Protter (Omasits et al., 2014). Residues in black are predicted to be involved in the catalytic mechanism.
Figure 3.
Figure 3.. Transmembrane topology of arsenic permeases.
While the number of predicted TMs for ArsB and ArsK (A) supports their classification as MFS transporters, other pumps such as Acr3 (A), ArsJ, and ArsP (B) are predicted to have fewer than 12 TMs. The ArsB and Acr3 topologies are based on experimental data. ArsJ, ArsP and ArsK topologies are predicted from in silico analysis. Transmembrane topology models were calculated with TMHMM and illustrated with Protter (Omasits et al., 2014). Residues in black are predicted to be involved in the catalytic mechanism.
Figure 4.
Figure 4.
A neighbor-joining phylogenetic tree showing the evolutionary relationship of MFS proteins encoded in ars operons. To obtain sequences of mfs1 genes encoding candidate orthologs, ArsJ (Shewanella putrefaciens 200), WP_014610147, was used for BLAST. To obtain sequences of mfs2 genes encoding candidate orthologs, ArsK (Agrobacterium tumefaciens GW4), KDR86814, was used for BLAST. To obtain sequences of mfs3 genes encoding candidate orthologs, MFS3 from Cupriavidus metallidurans CH34, WP_011515208, was used for BLAST. Only mfs genes in arsenic operons were included for phylogenetic analysis. ArsJ, predicted to transport the organorarsenical 1-arseno-3-phosphoglycerate (1As, 3PGA), is a found in the MFS1 branch. ArsK, which has broad substrate specificity for both inorganic and organic trivalent arsenicals, is found in the MFS2 branch. Substrates of MFS3 and MFS4 transporters have not yet been determined. The tree was produced by MEGA7. The bacterial species and protein accession numbers are shown.
Figure 5.
Figure 5.. Model of transporters.
As arsenic compounds adventitiously enter the cell through nutrient transporters such as aquaglyceroporins (AQP), glucose permeases (GLUT) or phosphate transporters (Pho), they are either directly extruded by specialized arsenic efflux pumps such as ArsB, Acr3, ArsK or ArsP, or are transformed by enzymes such as ArsC, ArsM, or GAPDH prior to efflux.

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