The top human NBD1–NBD2 dimer structure predicted by our
protein–protein approach is shown inFig. 2. Anotable feature of the
predicted structure is the head-to-tail conformation in which the
Walker A and B motifs of one NBD and the signature motif of the
other NBD formthe ATP-binding sites (seeFig. 1for the definition of
the motifs). The same unique dimeric mode is observed in the
recently solved crystal structures of the other ABC transporters (e.g.,
[40–44,15,45]). It should be emphasized that the protein–protein
docking process automatically predicted the heterodimer as
opposed to manually overlying other ABC transporters[13,12,14].
In other words, the head-to-tail conformation of NBDs is the most
stable binding orientation in terms of general protein–protein
interactions