NhaA family
| Na /H antiporter 1 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||||||
| Symbol | Na_H_antiport_1 | ||||||||||
| Pfam | PF06965 | ||||||||||
| InterPro | IPR004670 | ||||||||||
| TCDB | 2.A.36 | ||||||||||
| OPM superfamily | 106 | ||||||||||
| OPM protein | 1zcd | ||||||||||
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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.
Structure
[edit]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]
Function
[edit]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]
Na (in) 2H (out) ⇌ Na (out) 2H (in).
See also
[edit]References
[edit]- ^ 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. 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 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.
- ^ 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
[edit]- 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. 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 (BBA) - Bioenergetics. 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.
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