ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain [1].

The ABC module (approximately two hundred amino acid residues) is known to bind and hydrolyse ATP, thereby coupling transport to ATP hydrolysis in a large number of biological processes. The cassette is duplicated in several subfamilies. Its primary sequence is highly conserved, displaying a typical phosphate-binding loop: Walker A, and a magnesium binding site: Walker B. Besides these two regions, three other conserved motifs are present in the ABC cassette: the switch region which contains a histidine loop, postulated to polarise the attaching water molecule for hydrolysis, the signature conserved motif (LSGGQ) specific to the ABC transporter, and the Q-motif (between Walker A and the signature), which interacts with the gamma phosphate through a water bond. The Walker A, Walker B, Q-loop and switch region form the nucleotide binding site [2, 3, 4].

The 3D structure of a monomeric ABC module adopts a stubby L-shape with two distinct arms. ArmI (mainly beta-strand) contains Walker A and Walker B. The important residues for ATP hydrolysis and/or binding are located in the P-loop. The ATP-binding pocket is located at the extremity of armI. The perpendicular armII contains mostly the alpha helical subdomain with the signature motif. It only seems to be required for structural integrity of the ABC module. ArmII is in direct contact with the TMD. The hinge between armI and armII contains both the histidine loop and the Q-loop, making contact with the gamma phosphate of the ATP molecule. ATP hydrolysis leads to a conformational change that could facilitate ADP release. In the dimer the two ABC cassettes contact each other through hydrophobic interactions at the antiparallel beta-sheet of armI by a two-fold axis [5, 6, 7, 8, 9, 10].

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [11]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [11, 11]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [12, 12, 12]; (for further information see http://www.tcdb.org/tcdb/index.php?tc=3.A.1).

On the basis of sequence similarities a family of related ATP-binding proteins has been characterised [12, 13, 14, 15, 16].

The proteins belonging to this family also contain one or two copies of the 'A' consensus sequence [17] or the 'P-loop' [18].

1. Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. J. Mol. Evol. 48, 22-41
2. ABC transporters: physiology, structure and mechanism--an overview. Res. Microbiol. 152, 205-10
3. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8, 67-113
4. ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains. FEMS Microbiol. Rev. 22, 1-20
5. Structure and association of ATP-binding cassette transporter nucleotide-binding domains. Biochim. Biophys. Acta 1561, 47-64
6. Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure 9, 571-86
7. The crystal structure of the MJ0796 ATP-binding cassette. Implications for the structural consequences of ATP hydrolysis in the active site of an ABC transporter. J. Biol. Chem. 276, 32313-21
8. Crystal structure of the ATP-binding subunit of an ABC transporter. Nature 396, 703-7
9. Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis. EMBO J. 19, 5951-61
10. Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing. EMBO J. 20, 4964-72
11. The ABC of ABCS: a phylogenetic and functional classification of ABC systems in living organisms. Res. Microbiol. 152, 211-29
12. Binding protein-dependent transport systems. J. Bioenerg. Biomembr. 22, 571-92
13. A family of closely related ATP-binding subunits from prokaryotic and eukaryotic cells. Bioessays 8, 111-6
14. A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria. Nature 323, 448-50
15. Domainal evolution of a prokaryotic DNA repair protein and its relationship to active-transport proteins. Nature 323, 451-3
16. Structure and function of haemolysin B,P-glycoprotein and other members of a novel family of membrane translocators. Mol. Microbiol. 4, 873-80
17. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1, 945-51
18. The P-loop--a common motif in ATP- and GTP-binding proteins. Trends Biochem. Sci. 15, 430-4

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis
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