Biology:NhaA family

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Short description: Family of transport proteins
Na+/H+ antiporter 1
1zcd opm.png
Identifiers
SymbolNa_H_antiport_1
PfamPF06965
InterProIPR004670
TCDB2.A.36
OPM superfamily106
OPM protein1zcd

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).[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. "Projection structure of NhaA, a secondary transporter from Escherichia coli, at 4.0 A resolution". The EMBO Journal 18 (13): 3558–63. July 1999. doi:10.1093/emboj/18.13.3558. PMID 10393172. 
  2. "Three-dimensional structure of the ion-coupled transport protein NhaA". Nature 403 (6765): 112–5. January 2000. doi:10.1038/47534. PMID 10638764. Bibcode2000Natur.403..112W. 
  3. 3.0 3.1 "Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH". Nature 435 (7046): 1197–202. June 2005. doi:10.1038/nature03692. PMID 15988517. Bibcode2005Natur.435.1197H. 
  4. "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. February 2006. doi:10.1073/pnas.0510914103. PMID 16477015. Bibcode2006PNAS..103.2629O. 
  5. "Crucial steps in the structure determination of the Na+/H+ antiporter NhaA in its native conformation". Journal of Molecular Biology 362 (2): 192–202. September 2006. doi:10.1016/j.jmb.2006.07.019. PMID 16919297. 
  6. 6.0 6.1 6.2 "Mechanism of Na+/H+ antiporting". Science 317 (5839): 799–803. August 2007. doi:10.1126/science.1142824. PMID 17690293. Bibcode2007Sci...317..799A. 
  7. 7.0 7.1 "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. February 1993. doi:10.1073/pnas.90.4.1212. PMID 8381959. Bibcode1993PNAS...90.1212G. 
  8. 8.0 8.1 "The enlightening encounter between structure and function in the NhaA Na+-H+ antiporter". Trends in Biochemical Sciences 33 (9): 435–43. September 2008. doi:10.1016/j.tibs.2008.06.007. PMID 18707888. 
  9. "Cloning, functional expression and primary characterization of Vibrio parahaemolyticus K+/H+ antiporter genes in Escherichia coli". Molecular Microbiology 59 (2): 651–63. January 2006. doi:10.1111/j.1365-2958.2005.04966.x. PMID 16390457. 
  10. "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. October 2011. doi:10.1016/j.jmb.2011.08.046. PMID 21907722. 
  11. "2.A.33 The NhaA Na+:H+Antiporter (NhaA) Family". http://www.tcdb.org/search/result.php?tc=2.A.33. 

Further reading


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