title: The enlightening encounter between structure and function in the NhaA Na+-H+ antiporter.
abstract: Na(+)-H(+) antiporters are integral membrane proteins that exchange Na(+) for H(+) across the cytoplasmic membrane and many intracellular membranes. They are essential for Na(+), pH, and volume homeostasis, which are processes crucial for cell viability. Accordingly, antiporters are important drug targets in humans and underlie salt resistance in plants. Many Na(+)-H(+) antiporters are tightly regulated by pH. Escherichia coli NhaA, a prototype pH-regulated antiporter, exchanges 2H(+) for 1Na(+) (or Li(+)). The NhaA crystal structure has provided insight into the pH-regulated mechanism of antiporter action and revealed transmembrane segments, which are interrupted by extended mid-membrane chains that have since been found with variations in other ion-transport proteins. This novel structural fold creates a delicately balanced electrostatic environment in the middle of the membrane, which might be essential for ion binding and translocation.
authors: Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel. etana@vms.huji.ac.il
authors: Etana
authors: E
authors: Padan
mesh_terms: D027682:Cation Transport Proteins / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D017510:Protein Folding; D055503:Protein Multimerization; D012964:Sodium / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; C102839:NhaA protein, E coli; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium