Abstract
Recent studies performed on a series of Na+/H+ exchangers have led us to postulate a general mechanism for Na+/H+ exchange in the monovalent cation/proton antiporter superfamily. This simple mechanism employs a single binding site for which both substrates compete. The developed kinetic model is self-regulatory, ensuring down-regulation of transport activity at extreme pH, and elegantly explains the pH-dependent activity of Na+/H+ exchangers. The mechanism was experimentally verified and shown to describe both electrogenic and electroneutral exchangers. Using a small number of parameters, exchanger activity can be modeled under different conditions, providing insights into the physiological role of Na+/H+ exchangers.
References
Aronson, P.S., Nee, J., and Suhm, M.A. (1982). Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles. Nature 299, 161–163.10.1038/299161a0Suche in Google Scholar
Bobulescu, I.A., Di Sole, F., and Moe, O.W. (2005). Na+/H+ exchangers: physiology and link to hypertension and organ ischemia. Curr. Opin. Nephrol. Hypertens. 14, 485–494.10.1097/01.mnh.0000174146.52915.5dSuche in Google Scholar
Brett, C.L., Donowitz, M., and Rao, R. (2005). Evolutionary origins of eukaryotic sodium/proton exchangers. Am. J. Physiol. Cell Physiol. 288, C223–C239.10.1152/ajpcell.00360.2004Suche in Google Scholar
Calinescu, O., Danner, E., Bohm, M., Hunte, C., and Fendler, K. (2014a). Species differences in bacterial NhaA Na+/H+ exchangers. FEBS Lett. 588, 3111–3116.10.1016/j.febslet.2014.05.066Suche in Google Scholar
Calinescu, O., Paulino, C., Kuhlbrandt, W., and Fendler, K. (2014b). Keeping it simple, transport mechanism and pH regulation in Na+/H+ exchangers. J. Biol. Chem. 289, 13168–13176.10.1074/jbc.M113.542993Suche in Google Scholar
Donowitz, M., Ming Tse, C., and Fuster, D. (2013). SLC9/NHE gene family, a plasma membrane and organellar family of Na+/H+ exchangers. Mol. Aspects Med. 34, 236–251.10.1016/j.mam.2012.05.001Suche in Google Scholar
Goswami, P., Paulino, C., Hizlan, D., Vonck, J., Yildiz, O., and Kuhlbrandt, W. (2011). Structure of the archaeal Na+/H+ antiporter NhaP1 and functional role of transmembrane helix 1. EMBO J. 30, 439–449.10.1038/emboj.2010.321Suche in Google Scholar
Hunte, C., Screpanti, E., Venturi, M., Rimon, A., Padan, E., and Michel, H. (2005). Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH. Nature 435, 1197–1202.10.1038/nature03692Suche in Google Scholar
Jardetzky, O. (1966). Simple allosteric model for membrane pumps. Nature 211, 969–970.10.1038/211969a0Suche in Google Scholar
Kinsella, J.L. and Aronson, P.S. (1982). Determination of the coupling ratio for Na+ -H+ exchange in renal microvillus membrane vesicles. Biochim. Biophys. Acta 689, 161–164.10.1016/0005-2736(82)90200-0Suche in Google Scholar
Klingenberg, M. (1985a). Catalytic energy and carrier-catalyzed solute transport in biomembranes. In: Achievements and Perspectives of Mitochondrial Research, Vol. I, Bioenergetics, E. Quagliariello, E.C. Slater, F. Palmieri, C. Saccone, and A.M. Kroon, eds. (Amsterdam, New York, Oxford: Elsevier Science Publisher).Suche in Google Scholar
Klingenberg, M. (1985b). Principles of carrier catalysis elucidated by comparing two similar membrane translocators from mitochondria, the ADP/ATP carrier and the uncoupling protein. Ann. N.Y. Acad. Sci. 456, 279–288.10.1111/j.1749-6632.1985.tb14877.xSuche in Google Scholar PubMed
Klingenberg, M. (1992). Mechanistic and energetic aspects of carrier catalysis-exemplified with mitochondrial translocators. In: A Study of Enzymes, S.A. Kuby, ed. (Boca Raton, Ann Arbor, Boston: CRC Press).Suche in Google Scholar
Krulwich, T.A., Sachs, G., and Padan, E. (2011). Molecular aspects of bacterial pH sensing and homeostasis. Nat. Rev. Microbiol. 9, 330–343.10.1038/nrmicro2549Suche in Google Scholar PubMed PubMed Central
Landau, M., Herz, K., Padan, E., and Ben-Tal, N. (2007). Model structure of the Na+/H+ exchanger 1 (NHE1): functional and clinical implications. J. Biol. Chem. 282, 37854–37863.10.1074/jbc.M705460200Suche in Google Scholar PubMed
Leblanc, G., Bassilana, M., and Damiano-Forano, E. (1988). Na+/H+ exchange in bacteria and organelles. In: Na+/H+ Exchange, S. Grinstein and D. Piwnica-Worms, eds. (Boca Raton, Florida: CRC Press).Suche in Google Scholar
Lee, C., Kang, H.J., Von Ballmoos, C., Newstead, S., Uzdavinys, P., Dotson, D.L., Iwata, S., Beckstein, O., Cameron, A.D., and Drew, D. (2013). A two-domain elevator mechanism for sodium/proton antiport. Nature 501, 573–577.10.1038/nature12484Suche in Google Scholar PubMed PubMed Central
Lee, C., Yashiro, S., Dotson, D.L., Uzdavinys, P., Iwata, S., Sansom, M.S., Von Ballmoos, C., Beckstein, O., Drew, D., and Cameron, A.D. (2014). Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights. J. Gen. Physiol. 144, 529–544.10.1085/jgp.201411219Suche in Google Scholar PubMed PubMed Central
Lentes, C.J., Mir, S.H., Boehm, M., Ganea, C., Fendler, K., and Hunte, C. (2014). Molecular characterization of the Na+/H+-antiporter NhaA from Salmonella typhimurium. PLoS One 9, e101575.10.1371/journal.pone.0101575Suche in Google Scholar PubMed PubMed Central
Mager, T., Rimon, A., Padan, E., and Fendler, K. (2011). Transport mechanism and pH regulation of the Na+/H+ antiporter NhaA from Escherichia coli: an electrophysiological study. J. Biol. Chem. 286, 23570–23581.10.1074/jbc.M111.230235Suche in Google Scholar PubMed PubMed Central
Ohgaki, R., Van, I.S.C., Matsushita, M., Hoekstra, D., and Kanazawa, H. (2011). Organellar Na+/H+ exchangers: novel players in organelle pH regulation and their emerging functions. Biochemistry 50, 443–450.10.1021/bi101082eSuche in Google Scholar PubMed
Padan, E., Bibi, E., Ito, M., and Krulwich, T.A. (2005). Alkaline pH homeostasis in bacteria: new insights. Biochim. Biophys. Acta 1717, 67–88.10.1016/j.bbamem.2005.09.010Suche in Google Scholar PubMed PubMed Central
Padan, E., Kozachkov, L., Herz, K., and Rimon, A. (2009). NhaA crystal structure: functional-structural insights. J. Exp. Biol. 212, 1593–1603.10.1242/jeb.026708Suche in Google Scholar PubMed
Paulino, C. and Kuhlbrandt, W. (2014). pH- and sodium-induced changes in a sodium/proton antiporter. eLife 3, e01412.10.7554/eLife.01412Suche in Google Scholar PubMed PubMed Central
Paulino, C., Wohlert, D., Kapotova, E., Yildiz, O., and Kuhlbrandt, W. (2014). Structure and transport mechanism of the sodium/ proton antiporter MjNhaP1. eLife 3, e03583.10.7554/eLife.03583.029Suche in Google Scholar
Stein, W.D. and Honig, B. (1977). Models for active-transport of cations-steady-state analysis. Mol. Cell. Biochem. 15, 27–44.10.1007/BF01731287Suche in Google Scholar PubMed
Thauer, R.K., Kaster, A.K., Seedorf, H., Buckel, W., and Hedderich, R. (2008). Methanogenic archaea: ecologically relevant differences in energy conservation. Nat. Rev. Microbiol. 6, 579–591.10.1038/nrmicro1931Suche in Google Scholar PubMed
Wohlert, D., Yildiz, O., and Kuhlbrandt, W. (2014). Structure and substrate ion binding in the sodium/proton antiporter PaNhaP. eLife 3, e03579.10.7554/eLife.03579.026Suche in Google Scholar
©2015 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Meeting Report
- Membrane Transport and Communication in Frankfurt: Speakers’ Summary – Highlights
- HIGHLIGHT: MEMBRANE TRANSPORT AND COMMUNICATION
- Structure, function, evolution, and application of bacterial Pnu-type vitamin transporters
- Team work at its best – TAPL and its two domains
- The volume-regulated anion channel is formed by LRRC8 heteromers – molecular identification and roles in membrane transport and physiology
- Extending native mass spectrometry approaches to integral membrane proteins
- Functional diversity of the superfamily of K+ transporters to meet various requirements
- The structure of Na+-translocating of NADH:ubiquinone oxidoreductase of Vibrio cholerae: implications on coupling between electron transfer and Na+ transport
- Hybrid rotors in F1Fo ATP synthases: subunit composition, distribution, and physiological significance
- Homeostatic control of biological membranes by dedicated lipid and membrane packing sensors
- The transporter associated with antigen processing: a key player in adaptive immunity
- The pseudo-atomic structure of an RND-type tripartite multidrug efflux pump
- The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump
- A universal mechanism for transport and regulation of CPA sodium proton exchangers
- Biosynthesis of membrane dependent proteins in insect cell lysates: identification of limiting parameters for folding and processing
- Fluorescence and excited state dynamics of the deprotonated Schiff base retinal in proteorhodopsin
- Regulatory role of charged clusters in the N-terminal domain of BetP from Corynebacterium glutamicum
- The contribution of methionine to the stability of the Escherichia coli MetNIQ ABC transporter-substrate binding protein complex
- The ABC exporter MsbA probed by solid state NMR – challenges and opportunities
- Functional properties of LptA and LptD in Anabaena sp. PCC 7120
Artikel in diesem Heft
- Frontmatter
- Meeting Report
- Membrane Transport and Communication in Frankfurt: Speakers’ Summary – Highlights
- HIGHLIGHT: MEMBRANE TRANSPORT AND COMMUNICATION
- Structure, function, evolution, and application of bacterial Pnu-type vitamin transporters
- Team work at its best – TAPL and its two domains
- The volume-regulated anion channel is formed by LRRC8 heteromers – molecular identification and roles in membrane transport and physiology
- Extending native mass spectrometry approaches to integral membrane proteins
- Functional diversity of the superfamily of K+ transporters to meet various requirements
- The structure of Na+-translocating of NADH:ubiquinone oxidoreductase of Vibrio cholerae: implications on coupling between electron transfer and Na+ transport
- Hybrid rotors in F1Fo ATP synthases: subunit composition, distribution, and physiological significance
- Homeostatic control of biological membranes by dedicated lipid and membrane packing sensors
- The transporter associated with antigen processing: a key player in adaptive immunity
- The pseudo-atomic structure of an RND-type tripartite multidrug efflux pump
- The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump
- A universal mechanism for transport and regulation of CPA sodium proton exchangers
- Biosynthesis of membrane dependent proteins in insect cell lysates: identification of limiting parameters for folding and processing
- Fluorescence and excited state dynamics of the deprotonated Schiff base retinal in proteorhodopsin
- Regulatory role of charged clusters in the N-terminal domain of BetP from Corynebacterium glutamicum
- The contribution of methionine to the stability of the Escherichia coli MetNIQ ABC transporter-substrate binding protein complex
- The ABC exporter MsbA probed by solid state NMR – challenges and opportunities
- Functional properties of LptA and LptD in Anabaena sp. PCC 7120