Na+/H+ antiporter A (NhaA) family (TC# 2.A.33) contains a number of bacterial sodium-proton antiporter (SPAP) proteins. These are integral membrane proteins that catalyse the exchange of H+ for Na+ in a manner that is highly pH dependent. Homologues have been sequenced from a number of bacteria and archaea. Prokaryotes possess multiple paralogues. A representative list of the proteins that belong to the NhaA family can be found in the Transporter Classification Database.
Proteins of the NhaA family are of 300-700 amino acyl residues in length. NhaA of E. coli is a homeodimer, each subunit consisting of a bundle of 12 tilted transmembrane α-helices (TMSs).[1][2][3][4][5]
Molecular dynamics simulations of NhaA enabled proposal of an atomically detailed model of antiporter function.[6] Three conserved aspartate residues are key to this 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.[6][7][8]
Functionedit
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.[8][9] The E. coli protein probably functions in the regulation of the internal pH when the external pH is alkaline, and the protein effectively functions as a pH sensor.[7] It also uses the H+ gradient to expel Na+ from the cell. Its activity is highly pH dependent.[3][10]
The generalized transport reaction catalyzed by NhaA is:[6][11]
^Williams KA, Geldmacher-Kaufer U, Padan E, Schuldiner S, Kühlbrandt W (July 1999). "Projection structure of NhaA, a secondary transporter from Escherichia coli, at 4.0 A resolution". The EMBO Journal. 18 (13): 3558–63. doi:10.1093/emboj/18.13.3558. PMC1171434. PMID 10393172.
^Williams KA (January 2000). "Three-dimensional structure of the ion-coupled transport protein NhaA". Nature. 403 (6765): 112–5. Bibcode:2000Natur.403..112W. doi:10.1038/47534. PMID 10638764. S2CID 427512.
^ abHunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H (June 2005). "Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH". Nature. 435 (7046): 1197–202. Bibcode:2005Natur.435.1197H. doi:10.1038/nature03692. PMID 15988517. S2CID 4372674.
^Olkhova E, Hunte C, Screpanti E, Padan E, Michel H (February 2006). "Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications". Proceedings of the National Academy of Sciences of the United States of America. 103 (8): 2629–34. Bibcode:2006PNAS..103.2629O. doi:10.1073/pnas.0510914103. PMC1413810. PMID 16477015.
^Screpanti E, Padan E, Rimon A, Michel H, Hunte C (September 2006). "Crucial steps in the structure determination of the Na+/H+ antiporter NhaA in its native conformation". Journal of Molecular Biology. 362 (2): 192–202. doi:10.1016/j.jmb.2006.07.019. PMID 16919297.
^ abcArkin IT, Xu H, Jensen MØ, Arbely E, Bennett ER, Bowers KJ, Chow E, Dror RO, Eastwood MP, Flitman-Tene R, Gregersen BA, Klepeis JL, Kolossváry I, Shan Y, Shaw DE (August 2007). "Mechanism of Na+/H+ antiporting". Science. 317 (5839): 799–803. Bibcode:2007Sci...317..799A. doi:10.1126/science.1142824. PMID 17690293. S2CID 30745070.
^ abGerchman Y, Olami Y, Rimon A, Taglicht D, Schuldiner S, Padan E (February 1993). "Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 90 (4): 1212–6. Bibcode:1993PNAS...90.1212G. doi:10.1073/pnas.90.4.1212. PMC45842. PMID 8381959.
^ abPadan E (September 2008). "The enlightening encounter between structure and function in the NhaA Na+-H+ antiporter". Trends in Biochemical Sciences. 33 (9): 435–43. doi:10.1016/j.tibs.2008.06.007. PMID 18707888.
^Radchenko MV, Waditee R, Oshimi S, Fukuhara M, Takabe T, Nakamura T (January 2006). "Cloning, functional expression and primary characterization of Vibrio parahaemolyticus K+/H+ antiporter genes in Escherichia coli". Molecular Microbiology. 59 (2): 651–63. doi:10.1111/j.1365-2958.2005.04966.x. PMID 16390457. S2CID 22001614.
^Diab M, Rimon A, Tzubery T, Padan E (October 2011). "Helix VIII of NhaA Na(+)/H(+) antiporter participates in the periplasmic cation passage and pH regulation of the antiporter". Journal of Molecular Biology. 413 (3): 604–14. doi:10.1016/j.jmb.2011.08.046. PMID 21907722.
Appel M, Hizlan D, Vinothkumar KR, Ziegler C, Kühlbrandt W (February 2009). "Conformations of NhaA, the Na/H exchanger from Escherichia coli, in the pH-activated and ion-translocating states". Journal of Molecular Biology. 386 (2): 351–65. doi:10.1016/j.jmb.2008.12.042. PMID 19135453.
Herz K, Rimon A, Olkhova E, Kozachkov L, Padan E (January 2010). "Transmembrane segment II of NhaA Na+/H+ antiporter lines the cation passage, and Asp65 is critical for pH activation of the antiporter". The Journal of Biological Chemistry. 285 (3): 2211–20. doi:10.1074/jbc.M109.047134. PMC2804377. PMID 19923224.
Karpel R, Olami Y, Taglicht D, Schuldiner S, Padan E (July 1988). "Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli". The Journal of Biological Chemistry. 263 (21): 10408–14. doi:10.1016/S0021-9258(19)81531-4. PMID 2839489.
Padan E, Venturi M, Gerchman Y, Dover N (May 2001). "Na(+)/H(+) antiporters". Biochimica et Biophysica Acta. 1505 (1): 144–57. doi:10.1016/s0005-2728(00)00284-x. PMID 11248196.
Padan E, Danieli T, Keren Y, Alkoby D, Masrati G, Haliloglu T, Ben-Tal N, Rimon A (October 2015). "NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability". Proceedings of the National Academy of Sciences of the United States of America. 112 (41): E5575-82. Bibcode:2015PNAS..112E5575P. doi:10.1073/pnas.1510964112. PMC4611637. PMID 26417087.
Schushan M, Rimon A, Haliloglu T, Forrest LR, Padan E, Ben-Tal N (May 2012). "A model-structure of a periplasm-facing state of the NhaA antiporter suggests the molecular underpinnings of pH-induced conformational changes". The Journal of Biological Chemistry. 287 (22): 18249–61. doi:10.1074/jbc.M111.336446. PMC3365733. PMID 22431724.
As of this edit, this article uses content from "2.A.33 The NhaA Na+:H+Antiporter (NhaA) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.
January 01, 1970
nhaa, family, antiporter, nhaa, family, contains, number, bacterial, sodium, proton, antiporter, spap, proteins, these, integral, membrane, proteins, that, catalyse, exchange, manner, that, highly, dependent, homologues, have, been, sequenced, from, number, ba. Na H antiporter A NhaA family TC 2 A 33 contains a number of bacterial sodium proton antiporter SPAP proteins These are integral membrane proteins that catalyse the exchange of H for Na in a manner that is highly pH dependent Homologues have been sequenced from a number of bacteria and archaea Prokaryotes possess multiple paralogues A representative list of the proteins that belong to the NhaA family can be found in the Transporter Classification Database Na H antiporter 1IdentifiersSymbolNa H antiport 1PfamPF06965InterProIPR004670TCDB2 A 36OPM superfamily106OPM protein1zcdAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryPDB1zcd A 4 380 4CZ8 Contents 1 Structure 2 Function 3 See also 4 References 5 Further readingStructure editProteins of the NhaA family are of 300 700 amino acyl residues in length NhaA of E coli is a homeodimer each subunit consisting of a bundle of 12 tilted transmembrane a helices TMSs 1 2 3 4 5 Molecular dynamics simulations of NhaA enabled proposal of an atomically detailed model of antiporter function 6 Three conserved aspartate residues are key to this 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 6 7 8 Function editNa 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 8 9 The E coli protein probably functions in the regulation of the internal pH when the external pH is alkaline and the protein effectively functions as a pH sensor 7 It also uses the H gradient to expel Na from the cell Its activity is highly pH dependent 3 10 The generalized transport reaction catalyzed by NhaA is 6 11 Na in 2H out Na out 2H in See also editSodium Proton antiporter Antiporter Transporter Classification DatabaseReferences edit Williams KA Geldmacher Kaufer U Padan E Schuldiner S Kuhlbrandt W July 1999 Projection structure of NhaA a secondary transporter from Escherichia coli at 4 0 A resolution The EMBO Journal 18 13 3558 63 doi 10 1093 emboj 18 13 3558 PMC 1171434 PMID 10393172 Williams KA January 2000 Three dimensional structure of the ion coupled transport protein NhaA Nature 403 6765 112 5 Bibcode 2000Natur 403 112W doi 10 1038 47534 PMID 10638764 S2CID 427512 a b Hunte C Screpanti E Venturi M Rimon A Padan E Michel H June 2005 Structure of a Na H antiporter and insights into mechanism of action and regulation by pH Nature 435 7046 1197 202 Bibcode 2005Natur 435 1197H doi 10 1038 nature03692 PMID 15988517 S2CID 4372674 Olkhova E Hunte C Screpanti E Padan E Michel H February 2006 Multiconformation continuum electrostatics analysis of the NhaA Na H antiporter of Escherichia coli with functional implications Proceedings of the National Academy of Sciences of the United States of America 103 8 2629 34 Bibcode 2006PNAS 103 2629O doi 10 1073 pnas 0510914103 PMC 1413810 PMID 16477015 Screpanti E Padan E Rimon A Michel H Hunte C September 2006 Crucial steps in the structure determination of the Na H antiporter NhaA in its native conformation Journal of Molecular Biology 362 2 192 202 doi 10 1016 j jmb 2006 07 019 PMID 16919297 a b c Arkin IT Xu H Jensen MO Arbely E Bennett ER Bowers KJ Chow E Dror RO Eastwood MP Flitman Tene R Gregersen BA Klepeis JL Kolossvary I Shan Y Shaw DE August 2007 Mechanism of Na H antiporting Science 317 5839 799 803 Bibcode 2007Sci 317 799A doi 10 1126 science 1142824 PMID 17690293 S2CID 30745070 a b Gerchman Y Olami Y Rimon A Taglicht D Schuldiner S Padan E February 1993 Histidine 226 is part of the pH sensor of NhaA a Na H antiporter in Escherichia coli Proceedings of the National Academy of Sciences of the United States of America 90 4 1212 6 Bibcode 1993PNAS 90 1212G doi 10 1073 pnas 90 4 1212 PMC 45842 PMID 8381959 a b Padan E September 2008 The enlightening encounter between structure and function in the NhaA Na H antiporter Trends in Biochemical Sciences 33 9 435 43 doi 10 1016 j tibs 2008 06 007 PMID 18707888 Radchenko MV Waditee R Oshimi S Fukuhara M Takabe T Nakamura T January 2006 Cloning functional expression and primary characterization of Vibrio parahaemolyticus K H antiporter genes in Escherichia coli Molecular Microbiology 59 2 651 63 doi 10 1111 j 1365 2958 2005 04966 x PMID 16390457 S2CID 22001614 Diab M Rimon A Tzubery T Padan E October 2011 Helix VIII of NhaA Na H antiporter participates in the periplasmic cation passage and pH regulation of the antiporter Journal of Molecular Biology 413 3 604 14 doi 10 1016 j jmb 2011 08 046 PMID 21907722 2 A 33 The NhaA Na H Antiporter NhaA Family Transporter Classification Database Retrieved 2016 03 14 Further reading editAppel M Hizlan D Vinothkumar KR Ziegler C Kuhlbrandt W February 2009 Conformations of NhaA the Na H exchanger from Escherichia coli in the pH activated and ion translocating states Journal of Molecular Biology 386 2 351 65 doi 10 1016 j jmb 2008 12 042 PMID 19135453 Herz K Rimon A Olkhova E Kozachkov L Padan E January 2010 Transmembrane segment II of NhaA Na H antiporter lines the cation passage and Asp65 is critical for pH activation of the antiporter The Journal of Biological Chemistry 285 3 2211 20 doi 10 1074 jbc M109 047134 PMC 2804377 PMID 19923224 Karpel R Olami Y Taglicht D Schuldiner S Padan E July 1988 Sequencing of the gene ant which affects the Na H antiporter activity in Escherichia coli The Journal of Biological Chemistry 263 21 10408 14 doi 10 1016 S0021 9258 19 81531 4 PMID 2839489 Padan E Venturi M Gerchman Y Dover N May 2001 Na H antiporters Biochimica et Biophysica Acta 1505 1 144 57 doi 10 1016 s0005 2728 00 00284 x PMID 11248196 Padan E Danieli T Keren Y Alkoby D Masrati G Haliloglu T Ben Tal N Rimon A October 2015 NhaA antiporter functions using 10 helices and an additional 2 contribute to assembly stability Proceedings of the National Academy of Sciences of the United States of America 112 41 E5575 82 Bibcode 2015PNAS 112E5575P doi 10 1073 pnas 1510964112 PMC 4611637 PMID 26417087 Schushan M Rimon A Haliloglu T Forrest LR Padan E Ben Tal N May 2012 A model structure of a periplasm facing state of the NhaA antiporter suggests the molecular underpinnings of pH induced conformational changes The Journal of Biological Chemistry 287 22 18249 61 doi 10 1074 jbc M111 336446 PMC 3365733 PMID 22431724 Portal nbsp Biology As of this edit this article uses content from 2 A 33 The NhaA Na H Antiporter NhaA Family which is licensed in a way that permits reuse under the Creative Commons Attribution ShareAlike 3 0 Unported License but not under the GFDL All relevant terms must be followed Retrieved from https en wikipedia org w index php title NhaA family amp oldid 1170995718, wikipedia, wiki, book, books, library,
