ABC transporter
ContentsFunctionATP 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 yeast, 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). In humans the ABC transporters are classified into subfamilies, i.e. ABCB6 is ABC subfamily B member 6. ABC Transporters have two main functionalities 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].
For details of chloride transporter see CFTR (Hebrew). Structural highlightsTo 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 (GxxGxGKST) and B (ILLDEAT) 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].
DiseaseThere are currently 50 known ABC transporters in human. Of these there are 13 genetic diseases known to be associated with 14 of them. Among the diseases are cystic fibrosis, Stargardt disease, age-related macular degeneration and others. Mutations in CFTR lead to Cystic Fibrosis. 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].
| ||||||||||||
3D Structures of ABC transporter
Updated on 16-April-2018
- ABC amino acids transporters
- Arginine ABC transporter
- Transporters - CpABC arginine transporter, soluble domain (mutant) – Chlamydia pneumoniae
- 1l7v - CpABC arginine transporter, soluble domain
- Serotonin Transporter - CbABC arginine transporter + arginine – Coxiella burnetii
- Glut3 - GsABC amino acids transporter (mutant)+arginine - Geobacillus stearothermophilus
- Sanbox glut3 - ABC arginine transporter – Chlamydia trachomatis
- GLUT4 - SpABC amino acid transporter + arginine - Streptococcus pneumoniae
- Transporters - CpABC arginine transporter, soluble domain (mutant) – Chlamydia pneumoniae
- Branched amino acid ABC transporter
- Urea transporter - TtABC branched amino acids transporter (mutant)+valine – Thermus thermophilus
- CFTR (Hebrew) - SpABC branched-chain amino acids transporter
- 3tql, 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
- 3ip7 – AtABC valine transporter
- 3ipc – AtABC leucine transporter
- Urea transporter - TtABC branched amino acids transporter (mutant)+valine – Thermus thermophilus
- Lysine ABC transporter
- Histidine ABC transporter
- 2q2c - GsABC amino acids transporter (mutant)+histidine
- 2q2c - GsABC amino acids transporter (mutant)+histidine
- Glutamine ABC transporter
- Methionine ABC transporter
- 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
- 2qrr - ABC methionine transporter soluble domain - Vibrio parahaemolyticus
- 2qsw - EfABC methionine transporter C-terminal – Enterococcus faecalis
- Alanine ABC transporter
- Proline ABC transporter
- Polar amino acid ABC transporter
- 3hv1 - ABC polar amino acids transporter SBD – Streptococcus thermophilus
- 3hv1 - ABC polar amino acids transporter SBD – Streptococcus thermophilus
- Unspecified amino acid ABC transporter
- 3c41 - GsABC amino acids transporter +AMP-PNP
- 3c4j - GsABC amino acids transporter +ATPgS
- 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
- 3ip9 – AtABC amino acid transporter+GABA
- 3c41 - GsABC amino acids transporter +AMP-PNP
- 4z9n - ABC amino acid transporter+ glutathione – Brucella ovis
- Cationic amino acid ABC transporter
- 2m8c - EcABC amino acids transporter
- 2m8c - EcABC amino acids transporter
- Oligopeptide ABC transporter
- 3i5o, 1vr5 - TmABC oligopeptides transporter
- 4gl8 - BbABC oligopeptide transporter + peptide
- 4ikv, 4ikw - GkABC oligopeptides transporter – Geobacillus kaustophilus
- 4ikx, 4iky - GkABC oligopeptides transporter (mutant)
- 4ikz - GkABC oligopeptides transporter (mutant) + alafosfalin
- 2d5w - TtABC oligopeptide transporter + peptide
- 4gf8, 4gfr - VcABC oligopeptide transporter – Vibrio cholera
- 5yqw - ABC oligopeptide transporter – Vibrio harveyi
- 3i5o, 1vr5 - TmABC oligopeptides transporter
- Arginine ABC transporter
- ABC sugar transporters
- 2vk2 - EcABC galactofuranose transporter +galactofuranose
- 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
- 4qse - AfABC sugar transporter – Agrobacterium fabrum
- 4qrz - AfABC sugar transporter+maltotriose
- 4qsc - AfABC sugar transporter+maltose
- 4qsd - AfABC sugar transporter+sucrose
- 1vci, 1v43 - PhABC sugar transporter – Pyrococcus horikoshii
- 1oxx, 1oxs, 1oxt, 1oxu, 1oxv - ABC glucose transporter (mutant) – Sulfolobus solfataricus
- 3l49 - RsABC ribose transporter – Rhodobacter sphaeroides
- 4joq - RsABC ribose transporter (mutant)
- 3rot - ABC sugar transporter – Legionella pneumophila
- 4kvf - ABC rhamnose transporter – Kribbella flavida
- 4rxt - ArABC sugar transporter+ arabinose – Agrobacterium radiobacter
- 5iai - ArABC sugar transporter+ ribitol
- 5dvj, 5dvi, 5dvf - ABC sugar transporter+ monosaccharide – Pseudomonas putida
- 2vk2 - EcABC galactofuranose transporter +galactofuranose
- ABC maltose transporter see Maltose-binding protein
- ABC metal transporters
- ABC metal transporters
- 3hh8 - ABC metal transporter – Streptococcus pyogenes
- 3hh8 - ABC metal transporter – Streptococcus pyogenes
- ABC cobalt transporters
- 3gfo - ABC cobalt transporter – Clostridium perfringens
- 3gfo - ABC cobalt transporter – Clostridium perfringens
- ABC nickel transporters
- ABC tungsten transporters
- ABC iron transporters
- 3lhs, 3li2 - SaABC OpuAC ferrichrome transporter fragment+Staphyloferrin A
- 3mwf, 3mwg - SaABC siderophore transporter +Staphyloferrin B
- 3g9q, 3hxp - BsABC ferrichrome transporter
- 3be5, 3be6 - EcABC iron transporter
- 2etv - TmABC iron transporter
- 4h59, 4hmo, 4hmp, 4jcc - SpABC iron transporter
- 4hmq - SpABC iron transporter + ferrichrome
- 3lhs, 3li2 - SaABC OpuAC ferrichrome transporter fragment+Staphyloferrin A
- ABC molybdenum transporters
- ABC zinc transporters
- ABC metal transporters
- ABC multidrug transporters
- ABC choline transporters
- ABC α-hemolysin transporters
- ABC various compounds transporters
- 2v84 - ABC spermidine/putrescine transporter – Treponema pallidum
- 4eqb - SpABC spermidine/putrescine transporter
- 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 - VcABC phosphate transporter
- 4n13 - BbABC phosphate transporter (mutant)
- 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
- 4dve - LlABC biotin transporter + biotin
- 3uif – ABC sulfonate transporter – Methylobacillus flagellates
- 4mfi – ABC glycerol phosphate transporter – Mycobacterium tuberculosis
- 2q6h – AaABC serotonin transporter - Aquifex aeolicus
- 6an7, 6an5, 6amx – AaABC O-antigen polysaccharide transporter
- 6hnp – ABC O-antigen polysaccharide transporter – Raoultella ornithinolytica
- 2v84 - ABC spermidine/putrescine transporter – Treponema pallidum
- hABC transporters subfamilies
- ABC unspecified transporters
- 3lvu - SpABC transporter SBD
- 2ihy - SaABC transporter ATPase subunit
- 4k3v - SaABC transporter
- 3eaf - ABC transporter SBD – Aeropyrum pernix
- 3c9h - AtABC transporter – Agrobacterium tumefaciens
- 1vpl, 1ji0, 4q7k - TmABC transporter
- 2pcj, 2pcl - AaABC transporter
- 3rpw - ABC transporter – Rhodopseudomonas palustris
- 4ayt, 3zdq, 4ayt, 4ayw, 4ayx - hABC transporter B 10
- 4g68 – ABC transporter - Caldanaerobius
- 4wwh – ABC transporter + galactose – Mycobacterium smegmatis
- 3lvu - SpABC transporter SBD
- Cystic fibrosis transmembrane conductance regulator (CFTR)
- 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
- 3gd7 – hCFTR/malK+N6-phenylethyl-ATP
References
Proteopedia Page Contributors and Editors (what is this?)
Alexander Berchansky, Zina Saadi, Joel L. Sussman, Michal Harel