Computational study of the Na+/H + antiporter from Vibrio parahaemolyticus.
Sodium proton antiporters are ubiquitous membrane proteins that catalyze the exchange of Na(+) for protons throughout the biological world. The Escherichia coli NhaA is the archetypal Na(+)/H(+) antiporter and is absolutely essential for survival in high salt concentrations under alkaline conditions. Its crystal structure, accompanied by extensive molecular dynamics simulations, have provided an atomically detailed model of its mechanism. In this study, we utilized a combination of computational methodologies in order to construct a structural model for the Na(+)/H(+) antiporter from the gram-negative bacterium Vibrio parahaemolyticus. We explored its overall architecture by computational means and validated its stability and robustness. This protein belongs to a novel group of NhaA proteins that transports not only Na(+) and Li(+) as substrate ions, but K(+) as well, and was also found to miss a β-hairpin segment prevalent in other homologs of the Bacteria domain. We propose, for the first time, a structure of a prototype model of a β-hairpin-less NhaA that is selective to K(+). Better understanding of the Vibrio parahaemolyticus NhaA structure-function may assist in studies on ion transport, pH regulation and designing selective blockers.
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmund J. Safra Campus Givat-Ram, Jerusalem 91904, Israel. assaf.ganoth@mail.huji.ac.il
Assaf
A
Ganoth
Raphael
R
Alhadeff
Isaiah T
IT
Arkin
D000595:Amino Acid Sequence; D019295:Computational Biology; D004594:Electrophysiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D055550:Protein Stability; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014736:Vibrio parahaemolyticus / Q000235:genetics / Q000378:metabolism*
D017923:Sodium-Hydrogen Exchangers