Monovalent cation:proton antiporter-3
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.
A homologous, but only partially sequenced, system was earlier reported to catalyze Na+:H+ antiport in an alkalophilic Bacillus strain. PhaA and PhaD are respectively homologous to the ND5 and ND4 subunits of the H+-pumping NADH:ubiquinone oxidoreductase (TC #3.D.1). Homologous protein subunits from E. coli NADH:quinone oxidoreductase can functionally replace MrpA and MrpD in Bacillus subtilis.
Homologues of PhaA, B, C and D and Nha1, 2, 3 and 4 of an alkalophilic Bacillus strain are the Yuf(Mrp)T, U, V and D genes of Bacillus subtilis. In this system, YufT is believed to be responsible for Na+:H+ antiporter activity, but it does not have activity in the absence of other constituents of the operon.
The seven Pha proteins are of the following sizes (in #aas) and exhibit the following putative numbers of transmembrane α-helical spanners (TMSs):
- PhaA - 725 and 17
- PhaB - 257 and 5
- PhaC - 115 and 3
- PhaD - 547 and 13
- PhaE - 161 and 3
- PhaF - 92 and 3
- PhaG - 120 and 3
All are predicted to be integral membrane proteins.
- MnhA - 801 and 18
- MnhB - 142 and 4
- MnhC - 113 and 3
- MnhD - 498 and 13
- MnhE - 159 and 4
- MnhF - 97 and 3
- MnhG - 118 and 3
In view of the complexity of the system, large variation in subunit structure, and the homology with NDH family protein constituents, a complicated energy coupling mechanism, possibly involving a redox reaction, cannot be ruled out.
Na+ or Li+ does, but K+, Ca2+, and Mg2+ do not, support significant antiport by the Gram-positive bacterial systems (TC# 2.A.22.214.171.124 and TC# 2.A.126.96.36.199). Na+(Li+)/H+ antiporters have alkaline pH optima and apparent Km values for Na+ that are among the lowest reported for bacterial Na+/H+ antiporters. Na+/H+antiport consumes the pmf and therefore is probably electrogenic.
YufF (MrpF) appears to catalyze cholate efflux, possibly by a Na+ symport mechanism. It plays a major role in Na+ extrusion and is required for initiation of sporulation. Additionally, another component of the operon, MrpF (equivalent to PhaF of R. meliloti) has been implicated in choline and Na+ efflux. The MrpA-G proteins of B. subtilis have been shown to be present in a single multicomponent complex. They provide Na+/H+ antiport activity and function in multiple compound resistance and pH homeostasis.
The generalized reaction believed to be catalyzed by CPA3 family members is:
[K+ or Na+] (in) + H+ (out) ⇌ [K+ or Na+] (out) + H+ (in).
- Sodium-Proton antiporter
- Monovalent Cation (K+ or Na+):Proton Antiporter-1
- Monovalent Cation (K+ or Na+):Proton Antiporter-2
- Transporter Classification Database
- "2.A.63 The Monovalent Cation (K+ or Na+):Proton Antiporter-3 (CPA3) Family". Transporter Classification Databse. Retrieved 2016-03-16.
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- Kosono S, Morotomi S, Kitada M, Kudo T (January 1999). "Analyses of a Bacillus subtilis homologue of the Na+/H+ antiporter gene which is important for pH homeostasis of alkaliphilic Bacillus sp. C-125". Biochimica et Biophysica Acta. 1409 (3): 171–5. doi:10.1016/s0005-2728(98)00157-1. PMID 9878723.
- Hiramatsu T, Kodama K, Kuroda T, Mizushima T, Tsuchiya T (December 1998). "A putative multisubunit Na+/H+ antiporter from Staphylococcus aureus". Journal of Bacteriology. 180 (24): 6642–8. PMC 107768. PMID 9852009.
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- Ito M, Guffanti AA, Wang W, Krulwich TA (October 2000). "Effects of nonpolar mutations in each of the seven Bacillus subtilis mrp genes suggest complex interactions among the gene products in support of Na(+) and alkali but not cholate resistance". Journal of Bacteriology. 182 (20): 5663–70. doi:10.1128/jb.182.20.5663-5670.2000. PMC 94685. PMID 11004162.
- Kosono S, Ohashi Y, Kawamura F, Kitada M, Kudo T (February 2000). "Function of a principal Na(+)/H(+) antiporter, ShaA, is required for initiation of sporulation in Bacillus subtilis". Journal of Bacteriology. 182 (4): 898–904. doi:10.1128/jb.182.4.898-904.2000. PMC 94362. PMID 10648512.
- Ito M, Guffanti AA, Oudega B, Krulwich TA (April 1999). "mrp, a multigene, multifunctional locus in Bacillus subtilis with roles in resistance to cholate and to Na+ and in pH homeostasis". Journal of Bacteriology. 181 (8): 2394–402. PMC 93663. PMID 10198001.
- Kajiyama Y, Otagiri M, Sekiguchi J, Kosono S, Kudo T (October 2007). "Complex formation by the mrpABCDEFG gene products, which constitute a principal Na+/H+ antiporter in Bacillus subtilis". Journal of Bacteriology. 189 (20): 7511–4. doi:10.1128/JB.00968-07. PMC 2168430. PMID 17693497.
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