Phylogenetic and Functional Classification of Abc ( Atp - Binding Cassette ) Systems *

ATP-binding cassette (ABC) systems constitute one of the most abundant families of proteins. At the time of writing this review, we have identified more than 2000 ABC ATPase domains or proteins in translated nucleic acid sequence databases. A total of about 6000 proteins were found when the partners of ATPases were taken into account. The size of this mass of sequences is therefore similar to the coding capacity of a bacterial genome. Several properties of members of this superfamily have been reviewed in the last decade (Ames and Lecar, 1992; Ames et al., 1990, 1992; Doige and Ames, 1993; Higgins, 1992; Higgins et al., 1988; Holland and Blight, 1999). The most prominent characteristic of these systems is that they share a highly conserved ATPase domain, the ABC, which has been demonstrated to bind and hydrolyze ATP, thereby providing energy for a large number of biological processes. The amino acid sequence of this cassette displays three major conserved motifs, the Walker A and Walker B motifs commonly found in ATPases together with a specific signature motif, usually commencing LSGG-, and also known as the linker peptide (Schneider and Hunke, 1998). The crystal structures of some ABC proteins are presented in Chapters 4 and 7. ABC systems are involved not only in the import or export of a wide variety of substances, but also in many cellular processes and in their regulation. Importers constitute mainly the prokaryotic transporters dependent upon a substrate-binding protein (BPD), whose function is to provide bacteria with essential nutrients even if the latter are present in submicromolar concentrations in the environment (Boos and Lucht, 1996). Exporters are found in both prokaryotes and eukaryotes and are involved in the extrusion of noxious substances, the secretion of extracellular toxins and the targeting of membrane components (Fath and Kolter, 1993). The third type of ABC system is apparently not involved in transport but rather in cellular processes such as DNA repair, translation or regulation of gene expression. Since ATP is found principally in the cytosol, we define import as the inwardly directed transport of a molecule into the cytosol. By contrast, export is