NhaA family

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 1
Identifiers
SymbolNa_H_antiport_1
PfamPF06965
InterProIPR004670
TCDB2.A.36
OPM superfamily106
OPM protein1zcd
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1zcdA:4-380,4CZ8

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).[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

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

References
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. "2.A.33 The NhaA Na+:H+Antiporter (NhaA) Family". Transporter Classification Database. Retrieved 2016-03-14.

Further reading

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