2.A.34 The NhaB Na+:H+ Antiporter (NhaB) Family
NhaB homologues are of 513 to 528 amino acyl residues in length and possess about 12 transmembrane α-helical spanners (TMSs). They exhibit a region with limited sequence similarity to a 46 Kd membrane protein of unknown function from Mycobacterium leprae (spP46838) which is homologous to a member of arsenate resistance pumps of bacteria, archaea and eukaryotes (TC #3.A.4). Members of the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, and the Na+-translocating Mrp transporter superfamily can catalyze Na+/H+ antiiport (Patiño-Ruiz et al. 2022). Transport mechanisms for Na+/H+ exchangers that explain their highly pH-regulated activity profiles have been considered (Patiño-Ruiz et al. 2022).
The E. coli NhaB is 58% identical to the orthologous Vibrio alginolyticus Na+/H+ antiporter (Pinner et al., 1992). Although the latter protein is predicted to exhibit 10 TMSs, construction of NhaB-phoA fusions led to evidence for a 9 TMS model with the N-terminus in the cytoplasm and the C-terminus in the periplasm (Enomoto et al., 1998). A centrally located aspartyl residue in the 3rd TMS of the Vibrio alginolyticus homologue, conserved in all members of the family, has been shown to be essential for activity (Nakamura et al., 2001). The Klebsiella pneumoniae ortholog has also been studied in some detail, revealing stoichiomentric ratios in the wild type and mutant proteins (Patiño-Ruiz et al. 2017; Patiño-Ruiz et al. 2019).
The generalized transport reaction catalyzed by NhaB of E. coli is:
2 Na+ (in) + 3 H+ (out) ⇌ 2 Na+ (out) + 3 H+ (in)