2.A.12 The ATP:ADP Antiporter (AAA) Family

Members of the AAA family have been sequenced from bacteria and plants (Winkler and Neuhaus, 1999). One protein from the obligate intracellular bacterial parasite, Rickettsia prowazekii, the etiologic agent of the human disease epidemic typhus, is of 498 amino acyl residues and is believed to span the membrane 12 times (Alexeyev et al., 1999). The transporter is an obligate exchange translocase specific for ATP and ADP. It functions to take up ATP from the eukaryotic cell cytoplasm into the bacterium in exchange for ADP. The bacteria thus gains energy in the form of one pyrophosphate bond per ATP molecule taken up. Five AAA family paralogues are encoded within the genome of R. prowazekii. This organism transports UMP and GMP but not CMP, and it seems likely that one or more of the AAA family paralogues are responsible. Many other species of Rickettsia also possess AAA family homologues (Alexeyev et al., 1999). The ATP/ADP uniporters can also transport inorganic phosphate (Trentmann et al., 2008).

The AAA family proteins may be distantly related to members of the major facilitator superfamily (MFS; TC #2.A.1) and are not related to the mitochondrial ATP/ADP exchangers of the Mitochondrial Carrier Family (MCF; TC #2.A.5) which pump ATP out of mitochondria in accordance with the polarity of the mitochondrial membrane potential. However, two homologous adenylate translocators of the plant, Arabidopsis thaliana, have been sequenced and characterized. They are reported to be 589 and 569 amino acyl residues in length, possess twelve putative transmembrane spanners, and are about 85% identical to each other. They are about 44% identical to the rickettsial translocator described above. They are postulated to be localized to the intracellular plastid membrane where they function as ATP importers (Kampfenkel et al., 1995).

The genome of Chlamydia trachomatis encodes two AAA family members termed nucleoside-phosphate transporters 1 and 2, Npt1 and Npt2. They exhibit 68% and 61% similarity to the characterized R. prowazekii ATP:ADP antiporter. They similarly exhibit 12 putative TMSs. When expressed in E. coli, Npt1 catalyzed ATP:ADP exchange with KM values of 48 (ATP) and 30 (ADP) μM. No other nucleotides including AMP, GTP, dATP, CTP and UTP were transported. Ntp2 transported all four ribonucleoside triphosphates with KM values of 30 μM (GTP), 300 μM (UTP), 500 μM (CTP) and 1200 μM (ATP), probably employing a proton symport mechanism. Ribonucleoside di- and monophosphates as well as deoxyribonucleotides were not substrates (Tjaden et al., 1999).

The transport reaction catalyzed by the antiporters is:

ATP (out) + ADP (in) (+ energy?) ⇌ ATP (in) + ADP (out)

The transport reaction catalyzed by the proton symporter is probably:

NTP (out) + nH+ (out) → NTP (in) + nH+ (in)



This family belongs to the MFS Superfamily.

 

References:

Alexeyev, M.F. and H.H. Winkler. (1999). Membrane topology of the Rickettsia prowazekii ATP/ADP translocase revealed by novel dual pho-lac reporters. J. Mol. Biol. 285: 1503-1513.

Audia, J.P., and Winkler H.H. (2006). Study of the five Rickettsia prowazekii proteins annotated as ATP/ADP translocases (Tlc): Only Tlc1 transports ATP/ADP, while Tlc4 and Tlc5 transport other ribonucleotides. J. Bacteriol. 188: 6261-6268.

Conrath, U., C. Linke, W. Jeblick, P. Geigenberger, W.P. Quick, and H.E. Neuhaus. (2003). Enhanced resistance to Phytophthora infestans and Alternaria solani in leaves and tubers, respectively, of potato plants with decreased activity of the plastidic ATP/ADP transporter. Planta 217: 75-83.

Daugherty, R.M., N. Linka, J.P. Audia, C. Urbany, H.E. Neuhaus, and H.H. Winkler. (2004). The nucleotide transporter of Caedibacter caryophilus exhibits an extended substrate spectrum compared to the analogous ATP/ADP translocase of Rickettsia prowazekii. J. Bacteriol. 186: 3262-3265.

Fisher, D.J., R.E. Fernández, and A.T. Maurelli. (2013). Chlamydia trachomatis Transports NAD via the Npt1 ATP/ADP Translocase. J. Bacteriol. 195: 3381-3386.

Haferkamp, I., S. Schmitz-Esser, M. Wagner, N. Neigel, M. Horn, and H.E. Neuhaus. (2006). Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophila. Mol. Microbiol. 60: 1534-1545.

Kampfenkel, K., T. Möhlmann, O. Batz, M.V. Montagu, D. Inze, and H.E. Neuhaus. (1995). Molecular characterization of an Arabidopsis thaliana cDNA encoding a novel putative adenylate translocator of higher plants. FEBS Lett. 374: 351-355.

Linke, C., U. Conrath, W. Jeblick, T. Betsche, A. Mahn, K. Düring, and H.E. Neuhaus. (2002). Inhibition of the plastidic ATP/ADP transporter protein primes potato tubers for augmented elicitation of defense responses and enhances their resistance against Erwinia carotovora. Plant Physiol. 129: 1607-1615.

Möhlmann, T., J. Tjaden, C. Schwöppe, H.H. Winkler, K. Kampfenkel, and H.E. Neuhaus. (1998). Occurrence of two plastidic ATP/ADP transporters in Arabidopsis thaliana L.--molecular characterisation and comparative structural analysis of similar ATP/ADP translocators from plastids and Rickettsia prowazekii. Eur J Biochem 252: 353-359.

Neuhaus, H.E., E. Thom, T. Möhlmann, M. Steup, and K. Kampfenkel. (1997). Characterization of a novel eukaryotic ATP/ADP translocator located in the plastid envelope of Arabidopsis thaliana L. Plant J. 11: 73-82.

Plano, G.V. and H.H. Winkler. (1991). Identification and initial topological analysis of the Rickettsia prowazekii ATP/ADP translocase. J. Bacteriol. 173: 3389-3396

Schmitz-Esser, S., I. Haferkamp, S. Knab, T. Penz, M. Ast, C. Kohl, M. Wagner, and M. Horn. (2008). Lawsonia intracellularis contains a gene encoding a functional rickettsia-like ATP/ADP translocase for host exploitation. J. Bacteriol. 190: 5746-5752.

Tjaden, J., H.H. Winkler, C. Schwöppe, M. Van Der Laan, T. Möhlmann, and H.E. Neuhaus. (1999). Two nucleotide transport proteins in Chlamydia trachomatis, one for net nucleoside triphosphate uptake and the other for transport of energy. J. Bacteriol. 181: 1196-1202.

Trentmann, O., B. Jung, H.E. Neuhaus, and I. Haferkamp. (2008). Nonmitochondrial ATP/ADP transporters accept phosphate as third substrate. J. Biol. Chem. 283: 36486-36493.

Trentmann, O., M. Horn, A.C. van Scheltinga, H.E. Neuhaus, and I. Haferkamp. (2007). Enlightening energy parasitism by analysis of an ATP/ADP transporter from chlamydiae. PLoS. Biol 5: e231.

Tsaousis, A.D., E.R. Kunji, A.V. Goldberg, J.M. Lucocq, R.P. Hirt, and T.M. Embley. (2008). A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453: 553-556.

Vahling, C.M., Y. Duan, and H. Lin. (2010). Characterization of an ATP translocase identified in the destructive plant pathogen "Candidatus Liberibacter asiaticus". J. Bacteriol. 192: 834-840.

Williamson, L.R., G.V. Plano, H.H. Winkler, D.C. Krause, and D.O. Wood. (1989). Nucleotide sequence of the Rickettsia prowazekii ATP/ADP translocase-encoding gene. Gene 80: 260-278.

Winkler, H.H. (1976). Rickettsial permeability. An ADP-ATP transport system. J. Biol. Chem. 251: 389-396.

Winkler, H.H. and H.E. Neuhaus. (1999). Non-mitochondrial ATP transport. Trends Biol. Sci. 24: 64-68.

Winkler, H.H., R. Daugherty, and F. Hu. (1999). Rickettsia prowazekii transports UMP and GMP, but not CMP, as building blocks for RNA synthesis. J. Bacteriol. 181: 3238-3241.

Examples:

TC#NameOrganismal TypeExample
2.A.12.1.1ATP:ADP antiporter (transports ATP and ADP but not dATP, dADP, ddATP or ddADP), Tlc1 (Daugherty et al., 2004)Bacteria ATP/ADP translocase (Tlc1) of Rickettsia prowazekii (spP19568)
 
2.A.12.1.10The microsporidial ATP/ADP exchanger, NTT1 (Km= 11μM; cell surface localized when in the host cell; Tsaousis et al. 2008).

Fungi

NTT1 of Encephalitozoon cuniculi (Q8SRA2)

 
2.A.12.1.11The microsporidial ATP/ADP exchanger, NTT2 (Km= 20μM; present in spores; localized to the cell surface; Tsaousis et al., 2008).

Fungi

NTT2 of Encephalitozoon cuniculi (Q8SUF9)

 
2.A.12.1.12The microsporidial ATP/ADP exchanger, NTT3 (Km= 24μM; present in mitosomes; Tsaousis et al., 2008).

Fungi

NTT3 of Encephalitozoon cuniculi (Q8SUG0)

 
2.A.12.1.13The microsporidial ATP/ADP exchanger, NTT4 (Km= 2μM; present on the cell surface when in the host cell; Tsaousis et al., 2008).

Fungi

NTT4 of Encephalitozoon cuniculi (Q8SUG7)

 
2.A.12.1.14The nucleotide (ATP/ADP) exchanger NTT1 (Schmitz-Esser et al., 2008) (KMs for ATP and ADP ~ 250 μM)

δ-Proteo-bacteria

NTT1 of Lawsonia intracellularis (B0RZB7)

 
2.A.12.1.15

High affinity ATP/ADP antiporter of 469 aas and 12 TMSs, NttA.  Probably also transporters other nucleotides with low affinity (Vahling et al. 2010).

Proteobacteria

NttA of Liberibacter asiaticus (Citrus greening disease) (Liberobacter asiaticum)

 
2.A.12.1.16

ATP:ADP antiporter of 624 aas and 12 TMSs, AATP1. Transports ATP and ADP in a counterflow reaction.  The apparent Km value for ATP was reported to be 28 μM (Neuhaus et al. 1997). In Solanum tuberosum (potato), inhibition of the orthologous AATP1 transporter resulted in greater resistance to the soft rot-causing pathogen, Erwinia carotovora subsp. atroseptica (Linke et al. 2002) and the pathogenic fungus, Alternaria solani (Conrath et al. 2003).

Plants

Adenylate translocator-1 (AATP1) of Arabidopsis thaliana (gbZ49227)

 
2.A.12.1.17

Nucleoside triphosphate:H+ symporter.  Transports ATP, GTP, CTP and UTP (Tjaden et al. 1999).

Bacteria

Npt2 of Chlamydia trachomatis (gbAE001323)

 
2.A.12.1.18NAD+:ADP antiporter, Ntt4 (Haferkamp et al., 2006)Bacteria

Ntt4 of Candidatus Protochlamydia amoeboophila (Q6MDZ0)

 
2.A.12.1.19

Chloroplast inner envelope ATP/ADP antiporter, AATP2, of 618 aas and 12 TMSs. The apparent Km values for ATP and ADP were reported to be 22 μM and 20 μM, respectively. (Möhlmann et al. 1998).

AATP2 of Arabidopsis thaliana (Mouse-ear cress)

 
2.A.12.1.2

ATP:ADP antiporter, Npt1 (Tjaden et al. 1999).  Also transports NAD as a preferred substrate (Fisher et al. 2013).

Bacteria

Npt1 of Chlamydia trachomatis (gbAE001281)

 
2.A.12.1.3Nucleotide antiporter (binds and probably transports ATP, dATP, ddATP, ADP, dADP and ddADP (deoxy on the sugar moiety) but not AMP, UTP, CTP or GTP) (Daugherty et al., 2004)BacteriaNucleotide antiporter of Caedibacter caryophilus (CAD29686)
 
2.A.12.1.4The nucleotide (CTP, UTP, GDP) (GTP inhibits but is not transported) (Audia and Winkler, 2006)Bacteria Tlc4 of Rickettsia prowazekii (Q9ZD47)
 
2.A.12.1.5The GTP/GDP transporter, Tlc5 (Audia and Winkler, 2006)Bacteria Tlc5 of Rickettsia prowazekii (O05962)
 
2.A.12.1.6ATP/ADP antiporter, Ntt1 (Haferkamp et al., 2006; Trentmann et al., 2007)BacteriaNtt1 of Candidatus protochlamydia amoebophila (Q6MEM5)
 
2.A.12.1.7NTP (all four ribonucleoside triphosphates) antiporter, Ntt2 (Haferkamp et a;., 2006)Bacteria Ntt2 of Candidatus protochlamydia amoebophila (Q6MEN4)
 
2.A.12.1.8UTP:H+ symporter, Ntt3 (Haferkamp et al., 2006)BacteriaNtt3 of Candidatus protochlamydia amoebophila (Q6MEN5)
 
2.A.12.1.9GTP/ATP:H+ symporter, Ntt5 (Haferkamp et al., 2006)BacteriaNtt5 of Candidatus protochlamydia amoebophila (Q6MBI2)
 
Examples:

TC#NameOrganismal TypeExample
2.A.12.2.1

AAA family homologue of 927 aas with an N-terminal 12 TMS MFS domain and a C-terminal fairly hydrophilic "lipodomain" not recognized by CDD.

Chlamydiae

AAA family homologue of Chlamydia trachomatis

 
2.A.12.2.2

AAA family member of 878 aas with an N-terminal 12 TMS MFS domain and a long (~450 aa) hydrophilic extension containing at least one internal HEAT_2 domain.

Proteobacteria

AAA family member of Novosphingobium sp. PP1Y

 
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample