Ubiquitous Existence of Cation-Proton Antiporter and its Structurefunction Interplay: A Clinical Prospect

Sodium, potassium, and protons are the most important ions for life on earth, and their homeostasis is crucially needed for the survival of cells. The biological cells have developed a system that regulates and maintains the integrity of the cells by facilitating the exchange of these ions. These systems include the specific type of ion transporter membrane proteins such as cation-proton antiporters. Cation proton antiporters induce the active transport of cations like Na+, K+ or Ca+ across the cell membrane in exchange for protons (H+) and make the organism able to survive in alkaline conditions, high or fluctuating pH, stressed temperature or osmolarity. The secondary transporter proteins exploit the properties of various specific structural components to carry out efficient active transport. Ec-NhaA crystal structure was resolved at acidic pH at which the protein is downregulated, which discloses the presence of 12 transmembrane (TM) helices. This structural fold, the “NhaA fold,” is speculated to contribute to the cation-binding site and conformational alterations during transport in various antiporters. Irrespective of the variation in the composition of amino acids and lengths of proteins, several other members of the CPA family, such as NmABST, PaNhaP, and MjNhaP1, share the common structural features of the Ec-NhaA. The present review elucidates the existence of CPAs throughout all the kingdoms and the structural intercorrelation with their function. The interplay in the structurefunction of membrane transporter protein may be implemented to explore the plethora of biological events such as conformation, folding, ion binding and translocation etc.