2.A.81 The Aspartate:Alanine Exchanger (AAEx) Family
A single functionally characterized protein, the aspartate:alanine exchanger (AspT) of the Gram-positive lactic acid bacterium, Tetragenococcus halophila D10 serves to characterize the AAEx family (Abe et al., 2002). This organism takes up L-aspartate, decarboxylates it to L-alanine and CO2 in the cytoplasm, catalyzed by L-aspartate β-decarboxylase (AspD), and exports the L-alanine in a 1:1 exchange reaction with L-aspartate. AspT is a hydrophobic protein of 543 aas and 10 putative TMSs with two TrkA-C domains between TMSs 5 and 6. This protein has many Gram-negative and Gram-positive bacterial homologues of unknown function, and possibly one very distant homologue in the archaeon, Halobacterium sp. strain NRC-1. This protein (384 aas; 10-12 putative TMSs; AAC82885) includes a 54-residue region (residues 6-60) that shows 35% identity and 51% similarity with the ammonium transporter, Amt of Corynebacterium glutamicum (spP54146). These proteins exhibit an internal duplication with 5 or 6 TMSs per repeat element.
Because one more negative charge is brought in (aspartate) that is exported (alanine), the exchange transport process results in net charge movement, creating a membrane potential, negative inside. Further, decarboxylation of aspartate consumes a scalar proton and thus generates a pH gradient (basic inside). The resultant pmf can drive ATP synthesis via the F-type ATPase (TC #3.A.2). Other such exchangers generating a pmf are the prototypical oxalate/formate exchanger of the MFS (TC #3.A.1) as well as glutamate/γ-amino butyrate, malate/lactate, citrate/lactate and histidine/histamine exchangers (for references see Abe et al., 2002).
AspT has 10 transmembrane helices (TMS), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3 (Nanatani et al., 2007). The hydrophilic cytoplasmic loop of AspT possesses a sequence divergent TrkA_C domain.
The generalized transport reaction catalyzed by AspT is:
L-aspartate (out) + L-alanine (in) ⇌ L aspartate (in) + L-alanine (out)
The L-aspartate:L-alanine exchanger, AspT. A mutant, R76K, has higher activity than the AspT-WT (R76), whereas R76D and R76E have lower activity than AspT-WT. Thus, R76 is involved in AspT substrate transport (Suzuki et al. 2016).
Bacteria and archaea
AspT of Tetragenococcus halophila sp. D10 (Q8L3K8)
The putative cobalt porter, CbtD (Rodionov et al. 2003)
CbtD of Bacteroides fragilis (Q5LCC7)
Succinate exporter, SucE1. Induced under microaerobic and anaerobic conditions when succinate is produced from glucose via the reductive tricarboxylic acid cycle. Exhibits succinate counterflow (self exchange) (Fukui et al., 2011).
SucE1 of Corynebacterium glutamicum (Q8NNI8)
Putative transporter, YbjL
YbjL of E. coli
YidE of Escherichia coli
Aspartate:alanine antiporter, AspT, of 561 aas. AspT has 7 TMSs, a large cytoplasmic loop containing approximately 200 aas between TMS4 and TMS5, a cytoplasmic N-terminus, and a periplasmic C-terminus (Fujiki et al. 2007).
AspT of Pseudomonas dacunhae (Comamonas testosteroni)
Homologue of AspT (384 aas; 10 putative TMSs; with potential membrane embedded loops between TMSs 4 and 5 and TMSs 9 and 10 (the two halves are internally duplicated)). The central hydrophilic domain in 2.A.81.1.1 is absent in this homologue.
AspT homologue of Halobacterium sp. NRC-1 (AAC82885)
YidE/YbjL duplication protein
YidE homologue of Thermosipho melanesiensis