Mechanism of Na+/H+ Antiporting

by: Isaiah T Arkin, Huafeng Xu, Morten O Jensen, Eyal Arbely, Estelle R Bennett, Kevin J Bowers, Edmond Chow, Ron O Dror, Michael P Eastwood, Ravenna Flitman-Tene, Brent A Gregersen, John L Klepeis, Istvan Kolossvary, Yibing Shan, David E Shaw

Science, Vol. 317, No. 5839. (10 August 2007), pp. 799-803.

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Abstract

Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model. 10.1126/science.1142824

@article{citeulike:1661221, abstract = {Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model. 10.1126/science.1142824}, author = {Arkin, Isaiah T. and Xu, Huafeng and Jensen, Morten O. and Arbely, Eyal and Bennett, Estelle R. and Bowers, Kevin J. and Chow, Edmond and Dror, Ron O. and Eastwood, Michael P. and Flitman-Tene, Ravenna and Gregersen, Brent A. and Klepeis, John L. and Kolossvary, Istvan and Shan, Yibing and Shaw, David E. }, citeulike-article-id = {1661221}, doi = {http://dx.doi.org/10.1126/science.1142824}, journal = {Science}, keywords = {biomembranes, ion\_channels, molecular\_simulation}, month = {August}, number = {5839}, pages = {799--803}, posted-at = {2007-12-20 20:47:55}, priority = {0}, title = {Mechanism of Na+/H+ Antiporting}, url = {http://dx.doi.org/10.1126/science.1142824}, volume = {317}, year = {2007} }

RIS record

TY - JOUR ID - citeulike:1661221 L3 - citeulike-article-id:1661221 TI - Mechanism of Na+/H+ Antiporting JF - Science VL - 317 IS - 5839 SP - 799 EP - 803 N2 - Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model. 10.1126/science.1142824 KW - biomembranes KW - ion_channels KW - molecular_simulation AU - Arkin, Isaiah AU - Xu, Huafeng AU - Jensen, Morten AU - Arbely, Eyal AU - Bennett, Estelle AU - Bowers, Kevin AU - Chow, Edmond AU - Dror, Ron AU - Eastwood, Michael AU - Flitman-Tene, Ravenna AU - Gregersen, Brent AU - Klepeis, John AU - Kolossvary, Istvan AU - Shan, Yibing AU - Shaw, David PY - 2007/08/10/ UR - http://dx.doi.org/10.1126/science.1142824 ER -

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