Structural models of ABC transporters are based on the crystal structure of different bacterial proteins that act as importers such as vitamin B12 transporter BtuCDF from E. coli and exporters such as the multidrug exporter Sav1866 from Staphylococcus aureus or related flippases such as MsbA lipid flippase from E. coli [29,30,31]. On the basis of their architecture and biochemical activity, the ABC importers have been divided into type I and type II [12,32,33]. The energy coupling factor (ECF) transporters, which differ structurally and functionally from other ABC importers, are sometimes considered as type III ABC importers [34,35,36,37]. However, ABC importers have only been confirmed in prokaryotes, not in eukaryotes [11,15]; therefore, in this review, we focus only on ABC exporters.

The structure of ABC transporters is highly conserved among most eukaryotic organisms, including insects. A functional ABC transporter is characterized by the presence of a P-type traffic ATPase, which comprises two cytosolic nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs) [1,12,38] (Figure 1A). The four domains of a functional transporter (2TMDs-2NBDs) are combined in a single polypeptide, forming a full transporter (FT), whereas a half transporter (HT) contains one TMD and one NBD, which are sometimes encoded as separate polypeptides and then fused into multidomain proteins. For ATP binding and hydrolysis, the HT must become a functional transporter by forming homo- or heterodimeric complexes. The NBD contains several highly conserved nucleotide-binding sequences such as the Walker A and B motifs, common in nucleotide-binding proteins (the Walker B motif also provides the catalytic base); d-loop, which contains an aspartate residue and is responsible for forming a salt bridge; Q-loop, which contains a glutamate residue and acts as the attacking nucleophile in ATP hydrolysis; H motif, which has an invariant histidine active site that may be involved in maintaining the stability of the pre-hydrolytic state; and an α-helical region that has the ABC signature sequence (LSGGQ motif) [12,13,39]. The ABC exporter fold, a prominent quaternary structure in TMDs in all ABC exporters, is characterized by 12 transmembrane helices and acts as a switch between different conformational changes and initiates substrate translocation [12].

ABC transporters have a common mechanism for exporting substrates across the membrane by hydrolyzing ATP as a pump, but other models have been proposed for the ABC transporter mechanism based on structural and biochemical evidence, including the ATP-switch [39], alternating site [40], constant contact [41,42], and thermodynamic models [43]. Among these models, the ATP-switch model provides a reasonable framework for the transport mechanism [39,44,45] in which repeated communication between NBDs and TMDs occurs in both directions and involves only non-covalent conformational changes. The transport process is initiated by the binding of the substrate to the TMDs, and subsequent structural changes are transmitted to the NBDs, which include ATP-binding and closed dimer formation of the NBDs. Then the closed NBD dimer induces a substantial conformational change in the TMDs. This conformational change initiates translocation of the substrate through a rotation of the TMDs and opening toward the extracellular milieu. Finally, the ATP is hydrolyzed, releasing ADP and Pi and destabilizing the closed dimer conformation to restore its open dimer configuration for another new cycle [39,44,45] (Figure 1B).

In recent years, with the large-scale development of genome sequencing technology, the sequencing results have shown that ABC transporter genes are highly conserved in many insects (Figure 2). Aside from some important discoveries on the function of some ABC transporters in insects, however, knowledge on the role and function of these proteins is still limited. ABC transporters of numerous important agricultural pests and model insects, such as D. melanogaster, B. mori, Helicoverpa armigera and Plutella xylostella, have been reported (Table 1).