NhaA family

Last updated
Na+/H+ antiporter 1
1zcd opm.png
Identifiers
SymbolNa_H_antiport_1
Pfam PF06965
InterPro IPR004670
TCDB 2.A.36
OPM superfamily 106
OPM protein 1zcd
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1zcd A:4-380, 4CZ8

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.

Contents

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

Related Research Articles

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<span class="mw-page-title-main">Antiporter</span>

An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell. Na+/H+ antiporters have been reviewed.

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The ion transporter (IT) superfamily is a superfamily of secondary carriers that transport charged substrates.

The NhaB family belongs to the ion transporter (IT) superfamily. A representative list of proteins belonging to the NhaB family can be found in the Transporter Classification Database.

The NhaC family belongs to the Ion Transporter (IT) Superfamily. A representative list of proteins belonging to the NhaC family can be found in the Transporter Classification Database.

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The Monovalent Cation:Proton Antiporter-1 (CPA1) Family (TC# 2.A.36) is a large family of proteins derived from Gram-positive and Gram-negative bacteria, blue-green bacteria, archaea, yeast, plants and animals. The CPA1 family belongs to the VIC superfamily. Transporters from eukaryotes have been functionally characterized to catalyze Na+:H+ exchange. Their primary physiological functions are thought to be in (1) cytoplasmic pH regulation, extruding the H+ generated during metabolism, and (2) salt tolerance (in plants), due to Na+ uptake into vacuoles. Bacterial homologues have also been found to facilitate Na+:H+ antiport, but some also catalyze Li+:H+ antiport or Ca2+:H+ antiport under certain conditions.

The Monovalent Cation:Proton Antiporter-2 (CPA2) Family is a moderately large family of transporters belonging to the CPA superfamily. Members of the CPA2 family have been found in bacteria, archaea and eukaryotes. The proteins of the CPA2 family consist of between 333 and 900 amino acyl residues and exhibit 10-14 transmembrane α-helical spanners (TMSs).

The Monovalent Cation (K+ or Na+):Proton Antiporter-3 (CPA3) Family (TC# 2.A.63) is a member of the Na+ transporting Mrp superfamily. The CPA3 family consists of bacterial multicomponent K+:H+ and Na+:H+ antiporters. The best characterized systems are the PhaABCDEFG system of Sinorhizobium meliloti (TC# 2.A.63.1.1) that functions in pH adaptation and as a K+ efflux system, and the MnhABCDEFG system of Staphylococcus aureus (TC# 2.A.63.1.3) that functions as a Na+ efflux Na+:H+ antiporter.

<span class="mw-page-title-main">Shimon Schuldiner</span>

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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. 1 2 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. 1 2 3 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. 1 2 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. 1 2 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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