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
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).
Molecular dynamics simulations of NhaA enabled proposal of an atomically detailed model of antiporter function. Three conserved aspartate residues are key to this proposed mechanism: Asp (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.
Function
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. 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. It also uses the H gradient to expel Na from the cell. Its activity is highly pH dependent.
The generalized transport reaction catalyzed by NhaA is:
Na (in) + 2H (out) ⇌ Na (out) + 2H (in).
See also
References
- 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
- 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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