NhaA family
| Na+/H+ antiporter 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| Identifiers | |||||||||
| Symbol | Na_H_antiport_1 | ||||||||
| Pfam | PF06965 | ||||||||
| InterPro | IPR004670 | ||||||||
| TCDB | 2.A.36 | ||||||||
| OPM superfamily | 346 | ||||||||
| OPM protein | 1zcd | ||||||||
| |||||||||
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 NhaA crystal structure has provided insight into the pH-regulated mechanism of antiporter action and revealed transmembrane segments, which are interrupted by extended mid-membrane chains that have since been found with variations in other ion-transport proteins. This novel structural fold creates a delicately balance electrostatic environment in the middle of the membrane, which might be essential for ion binding and translocation.[3]
The generalized transport reaction catalyzed by NhaA is:[6][11]
Na+ (in) + 2H+ (out) ⇌ Na+ (out) + 2H+ (in).
Crystal Structures
PDB: 1ZCD, 3FI1, 4ATV, 4AU5
See also
Further reading
- Appel, Matthias; Hizlan, Dilem; Vinothkumar, Kutti R.; Ziegler, Christine; Kühlbrandt, Werner (2009-02-20). "Conformations of NhaA, the Na/H exchanger from Escherichia coli, in the pH-activated and ion-translocating states". Journal of Molecular Biology 386 (2): 351–365.doi:10.1016/j.jmb.2008.12.042. ISSN 1089-8638.PMID 19135453.
- Herz, Katia; Rimon, Abraham; Olkhova, Elena; Kozachkov, Lena; Padan, Etana (2010-01-15)."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): 2211–2220.doi:10.1074/jbc.M109.047134. ISSN 1083-351X.PMC 2804377. PMID 19923224.
- Karpel, R.; Olami, Y.; Taglicht, D.; Schuldiner, S.; Padan, E. (1988-07-25). "Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli". The Journal of Biological Chemistry 263 (21): 10408–10414. ISSN 0021-9258. PMID 2839489.
- Padan, E.; Venturi, M.; Gerchman, Y.; Dover, N. (2001-05-01). "Na(+)/H(+) antiporters". Biochimica et Biophysica Acta 1505 (1): 144–157. ISSN 0006-3002.PMID 11248196.
- Padan, Etana; Danieli, Tsafi; Keren, Yael; Alkoby, Dudu; Masrati, Gal; Haliloglu, Turkan; Ben-Tal, Nir; Rimon, Abraham (2015-10-13). "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): E5575–5582. doi:10.1073/pnas.1510964112. ISSN 1091-6490. PMC 4611637. PMID 26417087.
- Schushan, Maya; Rimon, Abraham; Haliloglu, Turkan; Forrest, Lucy R.; Padan, Etana; Ben-Tal, Nir (2012-05-25). "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): 18249–18261. doi:10.1074/jbc.M111.336446. ISSN 1083-351X.PMC 3365733. PMID 22431724.
References
- ↑ Williams, K. A.; Geldmacher-Kaufer, U.; Padan, E.; Schuldiner, S.; Kühlbrandt, W. (1999-07-01). "Projection structure of NhaA, a secondary transporter from Escherichia coli, at 4.0 A resolution". The EMBO journal. 18 (13): 3558–3563. doi:10.1093/emboj/18.13.3558. ISSN 0261-4189. PMC 1171434
. PMID 10393172. - ↑ Williams, K. A. (2000-01-06). "Three-dimensional structure of the ion-coupled transport protein NhaA". Nature. 403 (6765): 112–115. doi:10.1038/47534. ISSN 0028-0836. PMID 10638764.
- 1 2 3 Hunte, Carola; Screpanti, Emanuela; Venturi, Miro; Rimon, Abraham; Padan, Etana; Michel, Hartmut (2005-06-30). "Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH". Nature. 435 (7046): 1197–1202. doi:10.1038/nature03692. ISSN 1476-4687. PMID 15988517.
- ↑ Olkhova, Elena; Hunte, Carola; Screpanti, Emanuela; Padan, Etana; Michel, Hartmut (2006-02-21). "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): 2629–2634. doi:10.1073/pnas.0510914103. ISSN 0027-8424. PMC 1413810. PMID 16477015.
- ↑ Screpanti, Emanuela; Padan, Etana; Rimon, Abraham; Michel, Hartmut; Hunte, Carola (2006-09-15). "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. ISSN 0022-2836. PMID 16919297.
- 1 2 3 Arkin, Isaiah T.; Xu, Huafeng; Jensen, Morten Ø; Arbely, Eyal; Bennett, Estelle R.; Bowers, Kevin J.; Chow, Edmond; Dror, Ron O.; Eastwood, Michael P. (2007-08-10). "Mechanism of Na+/H+ antiporting". Science (New York, N.Y.). 317 (5839): 799–803. doi:10.1126/science.1142824. ISSN 1095-9203. PMID 17690293.
- 1 2 Gerchman, Y.; Olami, Y.; Rimon, A.; Taglicht, D.; Schuldiner, S.; Padan, E. (1993-02-15). "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): 1212–1216. doi:10.1073/pnas.90.4.1212. ISSN 0027-8424. PMC 45842. PMID 8381959.
- 1 2 Padan, Etana (2008-09-01). "The enlightening encounter between structure and function in the NhaA Na+-H+ antiporter". Trends in Biochemical Sciences. 33 (9): 435–443. doi:10.1016/j.tibs.2008.06.007. ISSN 0968-0004. PMID 18707888.
- ↑ Radchenko, Martha V.; Waditee, Rungaroon; Oshimi, Sawako; Fukuhara, Masahiro; Takabe, Teruhiro; Nakamura, Tatsunosuke (2006-01-01). "Cloning, functional expression and primary characterization of Vibrio parahaemolyticus K+/H+ antiporter genes in Escherichia coli". Molecular Microbiology. 59 (2): 651–663. doi:10.1111/j.1365-2958.2005.04966.x. ISSN 0950-382X. PMID 16390457.
- ↑ Diab, Mohammad; Rimon, Abraham; Tzubery, Tzvi; Padan, Etana (2011-10-28). "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): 604–614. doi:10.1016/j.jmb.2011.08.046. ISSN 1089-8638. PMID 21907722.
- ↑ "2.A.33 The NhaA Na+:H+Antiporter (NhaA) Family". Transporter Classification Database. Retrieved 2016-03-14.
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