Abstract
The LysE superfamily consists of transmembrane transport proteins that catalyze export of amino acids, lipids and heavy metal ions. Statistical means were used to show that it includes newly identified families including transporters specific for (1) tellurium, (2) iron/lead, (3) manganese, (4) calcium, (5) nickel/cobalt, (6) amino acids, and (7) peptidoglycolipids as well as (8) one family of transmembrane electron carriers. Internal repeats and conserved motifs were identified, and multiple alignments, phylogenetic trees and average hydropathy, amphipathicity and similarity plots provided evidence that all members of the superfamily derived from a single common 3-TMS precursor peptide via intragenic duplication. Their common origin implies that they share common structural, mechanistic and functional attributes. The transporters of this superfamily play important roles in ionic homeostasis, cell envelope assembly, and protection from excessive cytoplasmic heavy metal/metabolite concentrations. They thus influence the physiology and pathogenesis of numerous microbes, being potential targets of drug action.
Highlights
Members of the LysE superfamily have long been known to catalyze solute export [1]
We demonstrate that the previously established members of this superfamily are homologous to members of eight additional families: (i) tellurium ion resistance proteins (TerC); (ii) iron/lead transporters (ILT); (iii) Mn2+ exporters (MntP); (iv) Ca2+/H+ antiporters-2 (CaCA2); (v) Ni2+/Co2+ transporters (NicO); (vi) neutral amino acid transporters (NAAT); (vii) peptidoglycolipid
In addition to the three previously established LysE superfamily members (Table 1), eight families were analyzed in this study: (i) CaCA2 (TC# 2.A.106); (ii) MntP (TC# 2.A.107); (iii) ILT (TC# 2.A.108); (iv) TerC (TC# 2.A.109); (v) NAAT (TC# 2.A.95); (vi) NicO (TC# 2.A.113); (vii) GAP (TC# 2.A.116) and (viii) disulfide bond oxidoreductase D proteins (DsbD) (TC# 5.A.1) (Table 1)
Summary
Three families had been shown to comprise this novel superfamily: (i) L-lysine and L-arginine exporters (LysE); (ii) homoserine/threonine resistance proteins (RhtB); and (iii) cadmium ion resistance proteins (CadD) [1]. While LysE and RhtB proteins catalyze export of amino acids, the more distant CadD proteins are involved in efflux of the heavy metal ion, cadmium (Cd2+) [1,2,3]. Most members of these families share similar sizes, around 200 amino acyl residues, similar hydrophobicity plots indicative of 6 transmembrane α-helical segments (TMSs), high degrees of sequence similarity within but not between families and prokaryotic origins [1]. We demonstrate that the previously established members of this superfamily are homologous to members of eight additional families: (i) tellurium ion resistance proteins (TerC); (ii) iron/lead transporters (ILT); (iii) Mn2+ exporters (MntP); (iv) Ca2+/H+ antiporters-2 (CaCA2); (v) Ni2+/Co2+ transporters (NicO); (vi) neutral amino acid transporters (NAAT); (vii) peptidoglycolipid
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