|PROSITE documentation PDOC00185|
ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily which uses the hydrolysis of ATP to energize diverse biological systems. ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions 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 [2,3].
The ABC module (approximately two hundred amino acid residues) is known to bind and hydrolyze 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 (see <PDOC00017>), 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 polarize 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 γ phosphate through a water bond. The Walker A, Walker B, Q-loop and switch region form the nucleotide binding site [4,5,6].
The 3D structure of a monomeric ABC module adopts a stubby L-shape with two distinct arms (see <PDB:1B0U>). ArmI (mainly β-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 α 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 γ 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 β-sheet of armI by a two-fold axis [7,8,9,10,11,12].
Proteins known to belong to this family are classified in several functional subfamilies depending on the substrate used [E1].
All different types of transporters with a functional attribution are listed below (references are only provided for recently characterized proteins).
Active import transport system components:
Active export transport system components:
As a signature pattern for this class of proteins, we use a conserved region which is located between the 'A' and the 'B' motifs of the ATP-binding site. The profile we developed is directed against the conserved ABC module by covering the region between β strand 1 and α helix 9, including not only the conserved motifs but also structural elements found N and C terminal to them. Our profile also recognizes the UvrA family which is evolutionarily related to the ABC transporter family.Note:
The ATP-binding region is duplicated in araG, mdl, msrA, rbsA, tlrC, uvrA, yejF, Mdr's, CFTR, pmd1 and in EF-3. In some of those proteins, the above pattern only detect one of the two copies of the domain.Last update:
November 2003 / Text revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Holland I.B., Cole S.P.C., Kuchler K., Higgins C.F.|
|Source||(In) ABC proteins from bacteria to man, Academic Press, San Diego, (2003).|
|2||Authors||Holland I.B., Blight M.A.|
|Source||J. Mol. Biol. 293:381-399(1999).|
|3||Authors||Saurin W., Hofnung M., Dassa E.|
|Title||Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters.|
|Source||J. Mol. Evol. 48:22-41(1999).|
|Title||ABC transporters: physiology, structure and mechanism--an overview.|
|Source||Res. Microbiol. 152:205-210(2001).|
|Title||ABC transporters: from microorganisms to man.|
|Source||Annu. Rev. Cell Biol. 8:67-113(1992).|
|6||Authors||Schneider E., Hunke S.|
|Title||ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains.|
|Source||FEMS Microbiol. Rev. 22:1-20(1998).|
|Title||Structure and association of ATP-binding cassette transporter nucleotide-binding domains.|
|Source||Biochim. Biophys. Acta 1561:47-64(2002).|
|8||Authors||Karpowich N., Martsinkevich O., Millen L., Yuan Y.R., Dai P.L., MacVey K., Thomas P.J., Hunt J.F.|
|Title||Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter.|
|9||Authors||Yuan Y.R., Blecker S., Martsinkevich O., Millen L., Thomas P.J., Hunt J.F.|
|Title||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.|
|Source||J. Biol. Chem. 276:32313-32321(2001).|
|10||Authors||Hung L.W., Wang I.X., Nikaido K., Liu P.Q., Ames G.F., Kim S.H.|
|11||Authors||Diederichs K., Diez J., Greller G., Muller C., Breed J., Schnell C., Vonrhein C., Boos W., Welte W.|
|Source||EMBO J. 19:5951-5961(2000).|
|12||Authors||Gaudet R., Wiley D.C.|
|Source||EMBO J. 20:4964-4972(2001).|