Structure and function of yeast and fungal Na⁺ /H⁺ antiporters

Sodium proton antiporters (or sodium proton exchangers [NHEs]) are a critical family of membrane proteins that exchange sodium for protons across cell membranes. In yeast and plants, their primary function is to keep the sodium concentration low inside the cytoplasm. One class of NHE constitutively expressed in yeast is the plasma membrane Na⁺ /H⁺ antiporter, and another class is expressed on the endosomal/vacuolar membrane. At present, four bacterial plasma membrane antiporter structures are known and nuclear magnetic resonance structures are available for the membrane spanning transmembrane helices of mammalian and yeast NHEs. Additionally, a vast amount of mutational data are available on the role of individual amino acids and critical motifs involved in transport. We combine this information to obtain a more detailed picture of the yeast NHE plasma membrane protein and review mechanisms of transport, conserved motifs, unique residues important in function, and regulation of these proteins. The Na⁺ /H⁺ antiporter of Schizosaccharomyces pombe, SpNHE1, is an interesting model protein in an easy to study system and is representative of fungal Na⁺ /H⁺ antiporters. © IUBMB Life, 70(1):23-31, 2018.