Many ABC exporters are heterodimers encompassing asymmetric ATP binding sites. In these transport proteins, one ATP binding site – called the degenerate site – entails a non-canonical catalytic dyad and is impaired in ATP hydrolysis but not in nucleotide binding. It is therefore at the second ATP binding site – the so-called consensus site – where ATP is predominantly if not exclusively consumed. Recently, we have solved the crystal structure of TM287/288 from the thermophilic bacterium Thermotoga maritima, which is the first structural representative of an ABC exporter containing asymmetric ATP binding sites. The transporter was crystallized in its apo state as well as with AMP-PNP bound exclusively to the degenerate site. The substrate binding cavity is oriented towards the cell interior in both structures. In contrast to the inward-oriented structures of homodimeric ABC exporters (MsbA, ABCB10, Atm1) or heterodimeric ABC exporters with two consensus sites (P-glycoprotein) in which the NBDs are separated or twisted, we found that the NBDs of TM287/288 remain in close contact and do not shift in the NBD dimerization plane even in the absence of nucleotides. A comparison between the apo structure with the AMP-PNP bound structure suggested that the asymmetric ATP binding sites are conformationally coupled via the D-loops owing their name to a highly conserved aspartate residue. In functional assays we could demonstrate that nucleotide binding to the degenerate site modulates the ATPase activity at the consensus site and thus appears to play a regulatory role in the transport cycle.