ABC transporter
ATP Binding Cassette (ABC) Transporters are ATP-dependent membrane proteins critical for most aspects of cell physiology, including the uptake of nutrients (importers) and elimination of waste products and energy generation (exporters) which are predominantly expressed in excretory organs, such as the liver, intestine, blood-brain barrier, blood-testes barrier, placenta, and kidney[1][2]. There are many ABC Transporters in organisms, for instance, there are 28 in Saccharomyces,58 in Caenorhabditis, 51 in Drosophila,129 in Arabadopsis,and the 69 ABC transporters in E. coli account for almost 5% of its genomic coding capacity[3]. ABC transporter protein translocates substrates across membranes. It contains a Solute Binding Domain (SBD). CFTR (Cystic Fibrosis Transmembrane Regulator) translocates chloride and thiocyanate. It contains a nucleotide binding domain (NBD). Mutations in CFTR lead to Cystic Fibrosis. In humans the ABC transporters are classified into subfamilies, i.e. ABCB6 is ABC subfamily B member 6. The images at the left and at the right correspond to one representative ABC transporter, i.e. the crystal structure of B12 Bacterial ABC Transporter (1l7v).
FunctionFunction
ABC Transporters has two main functionality acting either as exporters or importers. ABC Exporters release bound drugs to the extracellular environment, while ABC Importers accept substrate molecules from their relevant substrate-binding proteins[4]. For instance the Vitamin B12 transporter BtuCD (PDB 1l7v) is a binding protein-dependent ABC transporter system that uses the power of ATP hydrolysis to pump vitamin B12 into the cytoplasm of E. coli[5].
ABC Exporters Use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs[4].
To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A and B motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family[2].
3D Structures of ABC transporter3D Structures of ABC transporter
Update November 2011
ABC amino acids transportersABC amino acids transporters
3g41 - CpABC arginine transporter, soluble domain (mutant) – Chlamydia pneumoniae
3n26 - CpABC arginine transporter, soluble domain
3tql - CbABC arginine transporter + arginine – Coxiella burnetii
3lkb - TtABC branched amino acids transporter (mutant)+valine – Thermus thermophilus
3k4u - ABC transporter + lysine – Wolinella succinogenes
3i6v - SpABC amino acids transporter + lysine – Silicibacter pomeroyi
3h5l - SpABC branched-chain amino acids transporter
1g9x, 1g6h, 1gaj - ABC branched-chain amino acids transporter – Methanocaldococcus jannaschii
3td9 - TmABC branched-chain amino acids transporter + phenylalanine - Thermotoga maritima
3i09, 3n0w - ABC branched amino acids transporter – Burkholderia mallei
3hv1 - ABC polar amino acids transporter SBD – Streptococcus thermophilus
3c41 - GsABC amino acids transporter +AMP-PNP – Geobacillus stearothermophilus
3c4j - GsABC amino acids transporter +ATPgS
2pvu - GsABC amino acids transporter (mutant)+lysine
2q2a - GsABC amino acids transporter (mutant)+arginine
2q2c - GsABC amino acids transporter (mutant)+histidine
2olj - EcABC amino acid transporter+ADP/Mg – Escherichia coli
2olk - EcABC amino acid transporter+ADP-beta-S
2ouk - EcABC amino acid transporter+sulfate
3o6p - EfABC amino acids transporter
3i5o, 1vr5 - TmABC oligopeptides transporter
3ip5, 3ipa – AtABC alanine transporter – Agrobacterium tumefaciens
3ip6 – AtABC proline transporter
3tmg - ABC proline transporter – Borrelia burgdorferi
[[[2qrr]] - ABC methionine transporter soluble domain - Vibrio parahaemolyticus
2qsw - EfABC methionine transporter C-terminal – Enterococcus faecalis
3ced - SaABC methionine transporter NIL domain - Staphylococcus aureus
3tqw - CbABC methionine transporter + methionine
3dhw - EcABC methionine transporter
3dhx - EcABC methionine transporter C2 domain
3ip7 – AtABC valine transporter
3ipc – AtABC leucine transporter
3ip9 – AtABC amino acid transporter+GABA
ABC sugar transportersABC sugar transporters
2vk2 - EcABC galactofuranose transporter +galactofuranose
2xz3 – EcABC maltose trasnsporter + maltose
3ob4 - EcABC maltose trasnsporter (mutant) + maltotriose
2w7y - SpABC sugar transporter+A-trisaccaride – Streptococcus pneumoniae
2i58 - SpABC sugar transporter+raffinose
2hq0, 2heu, 2hfb - SpABC sugar transporter
3g1w - BhABC sugar transporter – Bacillus halodurans
2z8d - BlABC lacto-N-biose transporter SBD+lacto-N-biose – Bifidobacterium longum
2z8e - BlABC lacto-N-biose transporter SBD+galacto-N-biose
2z8f - BlABC lacto-N-biose transporter SBD+lacto-N-tetraose
3c6q - TmABC sugar transporter (mutant)+beta-xylopyranose
2yyz, 2qvc, 2h3h, 2hpg, 2ghb - TmABC sugar transporter
2fn9 - TmABC sugar transporter (mutant)
2o7i - TmABC sugar transporter+cellobiose
2gha , 2fnc - TmABC sugar transporter+maltotriose
2fn8 - TmABC sugar transporter+ribose
1vci, 1v43 - PhABC sugar transporter – Pyrococcus horikoshii
1oxx, 1oxs, 1oxt, 1oxu, 1oxv - ABC glucose transporter (mutant) – Sulfolobus solfataricus
3l49 - ABC ribose transporter – Rhodobacter sphaeroides
ABC metal transportersABC metal transporters
3hh8 - ABC metal transporter – Streptococcus pyogenes
3gfo - ABC cobalt transporter – Clostridium perfringens
3t66 - BhABC nickel transporter (mutant)
3lr1 - ABC tungstate transporter – Geobacter sulfurreducens
3lhs, 3li2 - SaABC OpuAC ferrichrome transporter fragment+Staphyloferrin A
3mwf, 3mwg - SaABC siderophore transporter +Staphyloferrin B
3g9q - BsABC ferrichrome transporter
3be5, 3be6 - EcABC iron transporter
3d31 - MaABC sulfate/molybdate transporter – Methanosarcina acetivorans
3cfx - MaABC sulfate/molybdate transporter + WO4
3cfz - MjABC sulfate/molybdate transporter + WO4
3cg1 - ABC sulfate/molybdate transporter + WO4 – Pyrococcus furiosus
3cg3 - PhABC sulfate/molybdate transporter + WO4
2etv - TmABC iron transporter
2ogw - EcABC zinc transporter
2xh8 - SeABC zinc transporter (mutant) – Salmonella enterica
2xqv - SeABC zinc transporter + Zn
2xy4 - SeABC zinc transporter
2ov3, 2ov1, 1pq4 - SsABC zinc transporter – Synechocystis
2onk - AfABC molybdate/tungstate transporter+Mo/W binding protein – Archaeoglobus fulgidus
2onr - AfABC molybdate/tungstate transporter+Mo
2ons - AfABC molybdate/tungstate transporter+W
ABC multidrug transportersABC multidrug transporters
2onj - SaABC multidrug transporter+AMP-PNP
2hyd - SaABC multidrug transporter
1mv5 - LlABC multidrug transporter ATP binding domain – Lactococcus lactis
ABC choline transportersABC choline transporters
3hcq - SmABC choline transporter (mutant) – Sinorhizobium meliloti
2rin - SmABC choline transporter (mutant)+acetylcholine
2reg - SmABC choline transporter (mutant)+choline
2rej, 2rf1 - SmABC choline transporter (mutant)
3o66 – SaABC choline transporter
ABC alpha-hemolysin transportersABC alpha-hemolysin transporters
2pmk - EcABC alpha-hemolysin transporter+TNP-ADP
2ff7 - EcABC alpha-hemolysin transporter+ADP
2ffa, 2ffb - EcABC alpha-hemolysin transporter (mutant)+ADP
2fgj, 2fgk, 2xef - EcABC alpha-hemolysin transporter (mutant)+ATP
3b5j - EcABC alpha-hemolysin transporter (mutant)+TNP-ADP
ABC various compounds transportersABC various compounds transporters
2v84 - ABC spermidine/putrescine transporter – Treponema pallidum
2qi9 - EcABC vitamin B12 transporter+BtuD+BtuF
1l7v - EcABC vitamin B12 transporter+BtuD
3p7i, 3qk6, 3quj, 3s4u – EcABC alkylphosphonate transporter PHND + aminoethyl phosphonic acid
1twy - ABC phosphate transporter – Vibrio cholerae
3l6g, 3l6h – LlABC OpuAC betaine transporter SBD
2zzv - TtABC solute transporter+lactate+Ca
2zzw - TtABC solute transporter+lactate+Zn
2zzx - TtABC solute transporter+lactate
3gfv - BsABC petrobactin transporter – Bacillus subtilis
3bk7 – ABC ATP-binding – Pyrococcus abyssi
3ppn - BsABC multiple solute transporter
3ppo, 3ppp, 3ppq, 3ppr - BsABC multiple solute transporter + solute
3hn0 – ABC NO3 transporter – Parabacteroides distasonis
3rlb - LlABC vitamin B1 transporter + thiamin
hABC transporters subfamilieshABC transporters subfamilies
3nh6 – hABCB6 NBD
3nhb – hABCB6 NBD+ADP
3nh9 – hABCB6 NBD+ATP
3nha – hABCB6 NBD+ATP+Mg
ABC unspecified transportersABC unspecified transporters
3lvu - SpABC transporter SBD
2ihy - SaABC transporter ATPase subunit
3eaf - ABC transporter SBD – Aeropyrum pernix
3c9h - AtABC transporter – Agrobacterium tumefaciens
1vpl, 1ji0 - TmABC transporter
2pcj, 2pcl - ABC transporter – Aquifex aeolicus
3rpw - ABC transporter – Rhodopseudomonas palustris
2yl4 - hABC transporter 10
CFTRCFTR
3gd7 – hCFTR/malK+N6-phenylethyl-ATP
2pze, 2pzf, 2pzg – hCFTR NBD1
2bbo, 2bbs, 2bbt - hCFTR NBD1 (mutant)
1xmi, 2xmj, 1xmj - hCFTR NBD1 (mutant)+ATP
1xf9, 2xfa, 1xfa - mCFTR NBD1 (mutant) - mouse
1q3h - mCFTR NBD1+AMPPNP
1r0w - mCFTR NBD1
1r0x, 1r0z, 1r10 - mCFTR NBD1+ATP
1r0y - mCFTR NBD1+ADP
1ckw, 1ckx, 1cky, 1ckz – CFTR F508 region - NMR
ReferencesReferences
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