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).