SLC4A gene family proteins include bicarbonate transporters that move HCO(3)(-) across the plasma membrane and regulate intracellular pH and transepithelial movement of acid-base equivalents. These transporters are Cl/HCO(3) exchangers, electrogenic Na/HCO(3) cotransporters, electroneutral Na/HCO(3) cotransporters, and Na(+)-driven Cl/HCO(3) exchanger. Studies of the bicarbonate transporters in vitro and in vivo have demonstrated their physiological importance for acid-base homeostasis at the cellular and systemic levels. Recent advances in structure/function analysis have also provided valuable information on domains or motifs critical for regulation, ion translocation, and protein topology. This chapter focuses on the molecular mechanisms of ion transport along with associated structural aspects from mutagenesis of particular residues and from chimeric constructs. Structure/function studies have helped to understand the mechanism by which ion substrates are moved via the transporters. This chapter also describes some insights into the structure of SLC4A1 (AE1) and SLC4A4 (NBCe1) transporters. Finally, as some SLC4A transporters exist in concert with other proteins in the cells, the structural features associated with protein-protein interactions are briefly discussed.
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