Prokaryotic Na+/H+ Exchangers—Transport Mechanism and Essential Residues

Abstract

Na+/H+ exchangers are essential for Na+ and pH homeostasis in all organisms. Human Na+/H+ exchangers are of high medical interest, and insights into their structure and function are aided by the investigation of prokaryotic homologues. Most prokaryotic Na+/H+ exchangers belong to either the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, or the Na+-translocating Mrp transporter superfamily. Several structures have been solved so far for CPA and Mrp members, but none for the IT members. NhaA from E. coli has served as the prototype of Na+/H+ exchangers due to the high amount of structural and functional data available. Recent structures from other CPA exchangers, together with diverse functional information, have allowed elucidation of some common working principles shared by Na+/H+ exchangers from different families, such as the type of residues involved in the substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilies. Here, we review several aspects of prokaryotic Na+/H+ exchanger structure and function, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers. We also discuss the proposed transport mechanisms for Na+/H+ exchangers that explain their highly pH-regulated activity profile.

A step into the rare biosphere: genomic features of the new genus Terrihalobacillus and the new species Aquibacillus salsiterrae from hypersaline soils

“…( Holtmann et al, 2003 ; Zulkifli et al, 2010 ; Hoffmann and Bremer, 2016 ). Efflux of Na + is crucial for cell survival due to the toxicity produced by high cytoplasmatic concentration of this ion ( Patiño-Ruiz et al, 2022 ). Mrp multisubunit Na + /H + exchangers (K05565, K05566, K05567, K05568, K05569, K05570, and K05571), encoded by the mrpABCDEFG operon and detected in our genome dataset, have been shown to provide salt tolerance in Bacillus subtilis ( Ito et al, 1999 ), the slight halophile Halomonas zhaodongensis ( Meng et al, 2014 ), and the cyanobacteria Anabaena sp.…”

Biotin pathway in novel Fodinibius salsisoli sp. nov., isolated from hypersaline soils and reclassification of the genus Aliifodinibius as Fodinibius

“…(Zulkifli et al, 2010). Another ion homeostasis-related protein annotated in the genome of strain 1BSP15-2V2 T (K03313) is the NhaA Na + /H + antiporter, which plays a relevant role to avoid the toxicity of high cytoplasmatic Na + concentrations (Krulwich et al, 2011;Patiño-Ruiz et al, 2022). However, potassium and sodium fluxes are impractical mechanisms to deal with sustained high osmolarity (Hoffmann and Bremer, 2017).…”

Decoding Microbial Responses to Ammonia Shock Loads in Biogas Reactors through Metagenomics and Metatranscriptomics

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