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Vitamin B12 transporter, BtuCD PDB 1l7v Identifiers Symbol Pfam InterPro PROSITE SCOP SUPERFAMILY TCDB OPM superfamily OPM protein ABC_tran PF00005 [2] [3] [4]
[1]
IPR003439
3g5u
Available protein structures: Pfam PDB structures [10] [11] ; PDBe [12]
RCSB PDB
ATP-binding cassette transporters (ABC-transporter) are members of a protein superfamily that is one of the largest and most ancient families with representatives in all extant phyla from prokaryotes to humans.[14][15] ABC transporters are transmembrane proteins that utilize the energy of adenosine triphosphate (ATP) hydrolysis to carry out certain biological processes including translocation of various substrates across membranes and non-transport-related processes such as translation of RNA and DNA repair.[16][17] They transport a wide variety of substrates across extra- and intracellular membranes, including metabolic products, lipids and sterols, and drugs. Proteins are classified as ABC transporters based on the sequence and organization of their ATP-binding cassette (ABC) domain(s). ABC transporters are involved in tumor resistance, cystic fibrosis and a range of other inherited human diseases along with both bacterial (prokaryotic) and eukaryotic (including human) developement of resistance to multiple drugs.
Lipid flippase MsbA
Function
ABC transporters utilize the energy of ATP hydrolysis to transport various substrates across cellular membranes. They are divided into three main functional categories. In prokaryotes, importers mediate the uptake of nutrients into the cell. The substrates that can be transported include ions, amino acids, peptides, sugars, and other molecules that are mostly hydrophilic. The membrane-spanning region of the ABC transporter protects hydrophilic substrates from the lipids of the membrane bilayer thus providing a pathway across the cell membrane. Eukaryotes do not possess any importers. Exporters or effluxers, which are both present in prokaryotes and eukaryotes, function as pumps that extrude toxins and drugs out of the cell. In gram-negative bacteria, exporters transport lipids and some polysaccharides from the cytoplasm to the periplasm. The third subgroup of ABC proteins do not function as transporters, but are rather involved in translation and DNA repair processes.[16]
Bacterial ABC transporters are essential in cell viability, virulence, and pathogenicity.[16] Iron ABC uptake systems, for example, are important effectors of virulence.[18] Pathogens use siderophores, such as FepA, to scavenge iron that is in complex with high-affinity iron-binding proteins or erythrocytes. These are high-affinity iron-complexing molecules that are secreted by bacteria and reabsorb iron into iron-siderophore complexes. The chvE-gguAB gene in Agrobacterium tumefaciens encodes glucose and galactose importers that are also associated with virulence.[19][20] Transporters are extremely vital in cell survival such that they function as protein systems that counteract any undesirable change occurring in the cell. For instance, a potential lethal increase in osmotic strength is counterbalanced by activation of osmosensing ABC transporters that mediate uptake of solutes.[21] Other than functioning in transport, some bacterial ABC proteins are also involved in the regulation of several physiological processes.[16]
ATP-binding cassette transporter In bacterial efflux systems, certain substances that need to be extruded from the cell include surface components of the bacterial cell (e.g. capsular polysaccharides, lipopolysaccharides, and teichoic acid), proteins involved in bacterial pathogenesis (e.g. hemolysis, heme-binding protein, and alkaline protease), heme, hydrolytic enzymes, S-layer proteins, competence factors, toxins, antibiotics, bacteriocins, peptide antibiotics, drugs and siderophores.[22] They also play important roles in biosynthetic pathways, including extracellular polysaccharide biosynthesis[23] and cytochrome biogenesis.[24]
Structure
The common feature of all ABC transporters is that they consist of two distinct domains, the transmembrane domain (TMD) and the nucleotide-binding domain (NBD). The TMD, also known as membrane-spanning domain (MSD) or integral membrane (IM) domain, consists of alpha helices, embedded in the membrane bilayer. It recognizes a variety of substrates and undergoes conformational changes to transport the substrate across the membrane. The sequence and architecture of TMDs is variable, reflecting the chemical diversity of substrates that can be translocated. The NBD or ATP-binding cassette (ABC) domain, on the other hand, is located in the cytoplasm and has a highly conserved sequence. The NBD is the site for ATP binding.[29] In most exporters, the N-terminal transmembrane domain and the C-terminal ABC domains are fused as a single polypeptide chain, arranged as TMD-NBD-TMD-NBD. An example is the E. coli hemolysin exporter HlyB. Importers have an inverted organization, that is, NBD-TMD-NBD-TMD, where the ABC domain is N-terminal whereas the TMD is C-terminal, such as in the E. coli MacB protein responsible for macrolide [16][17] resistance.
[27]
The structural architecture of ABC [28] Structure of an ABC exporter: Sav1866 with bound nucleotide (PDB 2onj ) transporters consists minimally of two TMDs and two ABCs. Four individual polypeptide chains including two TMD and two NBD subunits, may combine to form a full transporter such as in the E. coli BtuCD[30][31] importer involved in the uptake of vitamin B12. Most exporters, such as in the multidrug exporter Sav1866[32] from Staphylococcus aureus, are made up of a homodimer consisting of two half transporters or monomers of a TMD fused to a nucleotide-binding domain (NBD). A full transporter is often required to gain functionality. Some ABC transporters have additional elements that contribute to the regulatory function of this class of proteins. In particular, importers have a high-affinity binding protein (BP) that specifically associates with the substrate in the periplasm for delivery to the appropriate ABC transporter. Exporters do not have the binding protein but have an intracellular domain (ICD) that joins the membrane-spanning helices and the ABC domain. The ICD is believed to be responsible for communication between the TMD and NBD.[29]
Mechanism of transport
ABC transporters are active transporters, that is, they require energy in the form of adenosine triphosphate (ATP) to translocate substrates across cell membranes. These proteins harness the energy of ATP binding and/or hydrolysis to drive conformational changes in the transmembrane domain (TMD) and consequently transports molecules.[57] Both ABC importers and exporters have a common mechanism in transporting substrates because of the similarities in their structures. The mechanism that describes the conformational changes associated with binding of substrate is the alternating-access model. In this model, the substrate binding site alternates between outward- and inward-facing conformations. The relative binding affinities of the two conformations for the substrate largely determines the net direction of transport. For importers, since translocation is directed from the periplasm to the cytoplasm, then the outward-facing conformation will have higher binding affinity for substrate. In contrast, the substrate binding affinity in exporters will be greater in the inward-facing conformation.[29] A model that describes the conformational changes in the nucleotide-binding domain (NBD) as a result of ATP binding and hydrolysis is the ATP-switch model. This model presents two principal conformations of the NBDs: formation of a closed dimer upon binding two ATP molecules and dissociation to an open dimer facilitated by ATP hydrolysis and release of inorganic phosphate (Pi) and adenosine diphosphate (ADP). Switching between the open and closed dimer conformations induces conformational changes in the TMD resulting in substrate translocation.[58]
ATP-binding cassette transporter The general mechanism for the transport cycle of ABC transporters has not been fully elucidated but substantial structural and biochemical data has accumulated to support a model in which ATP binding and hydrolysis is coupled to conformational changes in the transporter. The resting state of all ABC transporters has the NBDs in an open dimer configuration, with low affinity for ATP. This open conformation possesses a chamber accessible to the interior of the transporter. The transport cycle is initiated by binding of substrate to the high-affinity site on the TMDs, which induces conformational changes in the NBDs and enhances the binding of ATP. Two molecules of ATP bind, cooperatively, to form the closed dimer configuration. The closed NBD dimer induces a conformational change in the TMDs such that the TMD opens, forming a chamber with an opening opposite to that of the initial state. The affinity of the substrate to the TMD is reduced, thereby releasing the substrate. Hydrolysis of ATP follows and then sequential release of Pi and then ADP restores the transporter to its basal configuration. Although a common mechanism has been suggested, the order of substrate binding, nucleotide binding and hydrolysis, and conformational changes, as well as interactions between the domains is still [16][22][25][29][47][50][57][58][59][60][61] debated. Several groups studying ABC transporters have differing assumptions on the driving force of transporter function. It is generally assumed that ATP hydrolysis provides the principal energy input or power stroke for transport and that the NBDs operate alternately and are possibly involved in different steps in the transport cycle.[62] However, recent structural and biochemical data shows that ATP binding, rather than ATP hydrolysis, provides the power stroke. It may also be that since ATP binding triggers NBD dimerization, the formation of the dimer may represent the power stroke. In addition, some transporters have NBDs that do not have similar abilities in binding and hydrolyzing ATP and that the interface of the NBD dimer consists of two ATP binding pockets suggests a concurrent function of the two NBDs in the transport cycle.[58] Some evidence to show that ATP binding is indeed the power stroke of the transport cycle was reported.[58] It has been shown that ATP binding induces changes in the substrate-binding properties of the TMDs. The affinity of ABC transporters for substrates has been difficult to measure directly, and indirect measurements, for instance through stimulation of ATPase activity, often reflects other rate-limiting steps. Recently, direct measurement of vinblastine binding to permease-glycoprotein (P-glycoprotein) in the presence of nonhydrolyzable ATP analogs, e.g. 5-adenylyl---imidodiphosphate (AMP-PNP), showed that ATP binding, in the absence of hydrolysis, is sufficient to reduce substrate-binding affinity.[63] Also, ATP binding induces substantial conformational changes in the TMDs. Spectroscopic, protease accessibility and crosslinking studies have shown that ATP binding to the NBDs induces conformational changes in multidrug resistance-associated protein-1 (MRP1),[64] HisPMQ,[65] LmrA,[66] and Pgp.[67] Two dimensional crystal structures of AMP-PNP-bound Pgp showed that the major conformational change during the transport cycle occurs upon ATP binding and that subsequent ATP hydrolysis introduces more limited changes.[68] Rotation and tilting of transmembrane -helices may both contribute to these conformational changes. Other studies have focused on confirming that ATP binding induces NBD closed dimer formation. Biochemical studies of intact transport complexes suggest that the conformational changes in the NBDs are relatively small. In the absence of ATP, the NBDs may be relatively flexible, but they do not involve a major reorientation of the NBDs with respect to the other domains. ATP binding induces a rigid body rotation of the two ABC subdomains with respect to each other, which allows the proper alignment of the nucleotide in the active site and interaction with the designated motifs. There is strong biochemical evidence that binding of two ATP molecules can be cooperative, that is, ATP must bind to the two active site pockets before the NBDs can dimerize and form the closed, catalytically active conformation.[58]
ABC importers
Most ABC transporters that mediate the uptake of nutrients and other molecules in bacteria rely on a high-affinity solute binding protein (BP). BPs are soluble proteins located in the periplasmic space between the inner and outer membranes of gram-negative bacteria. Gram-positive microorganisms lack a periplasm such that their binding protein is often a lipoprotein bound to the external face of the cell membrane. Some gram-positive bacteria have BPs fused to the transmembrane domain of the transporter itself.[16] The first successful x-ray crystal structure of an intact ABC importer is the molybdenum transporter (ModBC-A) from Archaeoglobus fulgidus.[33] Atomic-resolution structures of three other bacterial importers, E. coli BtuCD,[30] E. coli maltose transporter (MalFGK2-E),[34] and the putative metal-chelate transporter of Haemophilus influenza, HI1470/1,[36] have also been determined. The structures provided detailed pictures of the interaction of the transmembrane and ABC domains as well as revealed two different conformations with an opening in two opposite directions. Another common feature of importers is that each NBD is bound to one TMD primarily through a short cytoplasmic helix of the TMD, the coupling helix. This portion of the EAA loop docks in a surface cleft formed between the RecA-like and helical ABC subdomains and lies approximately parallel to the membrane bilayer.[60]
ABC exporters
Prokaryotic ABC exporters are abundant and have close homologues in eukaryotes. This class of transporters is studied based on the type of substrate that is transported. One class is involved in the protein (e.g. toxins, hydrolytic enzymes, S-layer proteins, lantibiotics, bacteriocins, and competence factors) export and the other in drug efflux. ABC transporters have gained extensive attention because they contribute to the resistance of cells to antibiotics and anticancer agents by pumping drugs out of the cells.[16] In gram-negative organisms, ABC transporters mediate secretion of protein substrates across inner and outer membranes simultaneously without passing through the periplasm. This type of secretion is referred to as type I secretion which involves three components that function in concert: an ABC exporter, a membrane fusion protein (MFP), and an outer membrane factor (OMF). An example is the secretion of hemolysin (HlyA) from E. coli where the inner membrane ABC transporter HlyB interacts with an inner membrane fusion protein HlyD and an outer membrane facilitator TolC. TolC allows hemolysin to be transported across the two membranes, bypassing the periplasm.[22] Bacterial drug resistance has become an increasingly major health problem. One of the mechanisms for drug resistance is associated with an increase in antibiotic efflux from the bacterial cell. Drug resistance associated with drug efflux, mediated by P-glycoprotein, was originally reported in mammalian cells. In bacteria, Levy and colleagues presented the first evidence that antibiotic resistance was caused by active efflux of a drug.[69] P-glycoprotein is the best-studied efflux pump and as such has offered important insights into the mechanism of bacterial pumps.[16] Although some exporters transport a specific type of substrate, most transporters extrude a diverse class of drugs with varying structure.[25] These transporters are commonly called multi-drug resistant (MDR) ABC transporters and sometimes referred to as hydrophobic vacuum cleaners.[61]
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Sav1866
The first high-resolution structure reported for an ABC exporter was that of Sav1866 from Staphylococcus aureus.[25][70] Sav1866 is a homolog of multidrug ABC transporters. It shows significant sequence similarity to human ABC transporters of subfamily B that includes MDR1 and TAP1/TAP2. The ATPase activity of Sav1866 is known to be stimulated by cancer drugs such as doxorubicin, vinblastine and others,[71] which suggests similar substrate specificity to P-glycoprotein and therefore a possible common mechanism of substrate translocation. Sav1866 is a homodimer of half transporters, and each subunit contains an N-terminal TMD with six helices and a C-terminal NBD. The NBDs are similar in structure to those of other ABC transporters, in which the two ATP binding sites are formed at the dimer interface between the Walker A motif of one NBD and the LSGGQ motif of the other. The ADP-bound structure of Sav1866 shows the NBDs in a closed dimer and the TM helices split into two wings oriented towards the periplasm, forming the outward-facing conformation. Each wing consists of helices TM1-2 from one subunit and TM3-6 from the other subunit. It contains long intracellular loops (ICLs or ICD) connecting the TMDs that extend beyond the lipid bilayer into the cytoplasm and interacts with the 8=D. Whereas the importers contain a short coupling helix that contact a single NBD, Sav1866 has two intracellular coupling helices, one (ICL1) contacting the NBDs of both subunits and the other (ICL2) interacting with only the opposite NBD subunit.[29][32][60]
MsbA
MsbA is a multi-drug resistant (MDR) ABC transporter and possibly a lipid flippase. It is an ATPase that transports lipid A, the hydrophobic moiety of lipopolysaccharide (LPS), a glucosamine-based saccharolipid that makes up the outer monolayer of the outer membranes of most gram-negative bacteria. Lipid A is an endotoxin and so loss of MsbA from the cell membrane or mutations that disrupt transport results in the accumulation of lipid A in the inner cell membrane resulting to cell death. It is a close bacterial homolog of P-glycoprotein (Pgp) by protein sequence homology and has overlapping substrate specificities with the MDR-ABC transporter LmrA from Lactococcus lactis.[72] MsbA from E. coli is 36% identical to the NH2-terminal half of human MDR1, suggesting a common mechanism for transport of amphiphatic and hydrophobic substrates. The MsbA gene encodes a half transporter that contains a transmembrane domain (TMD) fused with a nucleotide-binding domain (NBD). It is assembled as a homodimer with a total molecular mass of 129.2 kD. MsbA contains 6 TMDs on the periplasmic side, an NBD located on the cytoplasmic side of the cell membrane, and an intracellular domain (ICD), bridging the TMD and NBD. This conserved helix extending from the TMD segments into or near the active site of the NBD is largely responsible for crosstalk between TMD and NBD. In particular, ICD1 serves as a conserved pivot about which the NBD can rotate, therefore allowing the NBD to disassociate and dimerize during ATP binding and
ATP-binding cassette transporter hydrolysis.[16][22][25][29][50][60][61][73] Previously published (and now retracted) X-ray structures of MsbA were inconsistent with the bacterial homolog Sav1866.[77][78] The structures were reexamined and found to have an error in the assignment of the hand resulting to incorrect models of MsbA. Recently, the errors have [74] Structures of MsbA depicting the three conformational states: open apo (PDB 3b5w ), been rectified and new structures have [75] [76] [47] closed apo (PDB 3b5x ), and nucleotide-bound (PDB 3b60 ) been reported. The resting state of E. coli MsbA exhibits an inverted V shape with a chamber accessible to the interior of the transporter suggesting an open, inward-facing conformation. The dimer contacts are concentrated between the extracellular loops and while the NBDs are ~50 apart, the subunits are facing each other. The distance between the residues in the site of the dimer interface have been verified by cross-linking experiments[79] and EPR spectroscopy studies.[80] The relatively large chamber allows it to accommodate large head groups such as that present in lipid A. Significant conformational changes are required to move the large sugar head groups across the membrane. The difference between the two nucleotide-free (apo) structures is the ~30 pivot of TM4/TM5 helices relative to the TM3/TM6 helices. In the closed apo state (from V. cholerae MsbA), the NBDs are aligned and although closer, have not formed an ATP sandwich, and the P loops of opposing monomers are positioned next to one another. In comparison to the open conformation, the dimer interface of the TMDs in the closed, inward-facing conformation has extensive contacts. For both apo conformations of MsbA, the chamber opening is facing inward. The structure of MsbA-AMP-PNP (5-adenylyl---imidodiphosphate), obtained from S. typhimurium, is similar to Sav1866. The NBDs in this nucleotide-bound, outward-facing conformation, come together to form a canonical ATP dimer sandwich, that is, the nucleotide is situated in between the P-loop and LSGGQ motif. The conformational transition from MsbA-closed-apo to MsbA-AMP-PNP involves two steps which are more likely concerted: a ~10 pivot of TM4/TM5 helices towards TM3/TM6, bringing the NBDs closer but not into alignment followed by tilting of TM4/TM5 helices ~20 out of plane. The twisting motion results in the separation of TM3/TM6 helices away from TM1/TM2 leading to a change from an inward- to an outward- facing conformation. Thus, changes in both the orientation and spacing of the NBDs dramatically rearrange the packing of transmembrane helices and effectively switch access to the chamber from the inner to the outer leaflet of the membrane.[47] The structures determined for MsbA is basis for the tilting model of transport.[25] The structures described also highlight the dynamic nature of ABC exporters as also suggested by fluorescence and EPR studies.[60][80][81]
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Physiological role
In addition to conferring MDR in tumor cells, ABC transporters are also expressed in the membranes of healthy cells, where they facilitate the transport of various endogenous substances, as well as of substances foreign to the body. For instance, ABC transporters such as Pgp, the MRPs and BCRP limit the absorption of many drugs from the intestine, and pump drugs from the liver cells to the bile as a means of removing foreign substances from the body. A large number of drugs are either transported by ABC transporters themselves or affect the transport of other drugs. The latter scenario can lead to drug-drug interactions, sometimes resulting in altered effects of the drugs.[84]
Membrane assays
The vesicular transport assay detects the translocation of molecules by ABC transporters.[89] Membranes prepared under suitable conditions contain inside-out oriented vesicles with the ATP binding site and substrate binding site of the transporter facing the buffer outside. Substrates of the transporter are taken up into the vesicles in an ATP dependent manner. Rapid filtration using glass fiber filters or nitrocellulose membranes are used to separate the vesicles from the incubation solution and the test compound trapped inside the vesicles is retained on the filter. The quantity of the transported unlabelled molecules is determined by HPLC, LC/MS, LC/MS/MS. Alternatively, the compounds are radiolabeled, fluorescent or have a fluorescent tag so that the radioactivity or fluorescence retained on the filter can be quantified. Various types of membranes from different sources (e.g. insect cells, transfected or selected mammalian cell lines) are used in vesicular transport studies. Membranes are commercially available [90] or can be prepared from various cells or even tissues e.g. liver canalicular membranes. This assay type has the advantage of measuring the actual disposition of the substrate across the cell membrane. Its disadvantage is that compounds with medium-to-high passive permeability are not retained inside the vesicles making direct transport measurements with this class of compounds difficult to perform. The vesicular transport assay can be performed in an indirect setting, where interacting test drugs modulate the transport rate of a reporter compound. This assay type is particularly suitable for the detection of possible drug-drug interactions and drug-endogenous substrate interactions. It is not sensitive to the passive permeability of the compounds and therefore detects all interacting compounds. Yet, it does not provide information on whether the compound tested is an inhibitor of the transporter, or a substrate of the transporter inhibiting its function in a competitive fashion. A typical example of an indirect vesicular transport assay is the detection of the inhibition of
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Subfamilies
Human subfamilies
There are 48 known ABC transporters present in humans, which are classified into seven families by the Human Genome Organization.
Family ABCA Members This family contains some of the largest transporters (over 2,100 amino acids long). Five of them are located in a cluster in the 17q24 chromosome. Consists of 4 full and 7 half transporters. Function Responsible for the transportation of cholesterol and lipids, among other things. Examples ABCA12 ABCA1
ABCB
Some are located in the bloodbrain barrier, liver, mitochondria and transports peptides and bile, for example. Used in ion transport, cell-surface receptors, toxin secretion. Includes the CFTR protein, which causes cystic fibrosis when deficient. Are all used in peroxisomes.
ABCB5
ABCC
ABCC6
ABCD
ABCD1
These are not actually transporters but merely ATP-binding ABCE, domains that were derived from the ABC family, but without the ABCF1, transmembrane domains. These proteins mainly regulate protein ABCF2 synthesis or expression. Transports lipids, diverse drug substrates, bile, cholesterol, and other steroids. ABCG2 ABCG1-
ABCG
Consists of 6 reverse half-transporters, with the NBF at the NH3+ end and the TM at the COOend.
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Prokaryotic subfamilies
Importers Carbohydrate Uptake Transporter-1 (CUT1) Carbohydrate Uptake Transporter-2 (CUT2) Polar Amino Acid Uptake Transporter (PAAT) Peptide/Opine/Nickel Uptake Transporter (PepT) Hydrophobic Amino Acid Uptake Transporter (HAAT) Sulfate/Tungstate Uptake Transporter (SulT) Phosphate Uptake Transporter (PhoT) Molybdate Uptake Transporter (MolT) Phosphonate Uptake Transporter (PhnT) Ferric Iron Uptake Transporter (FeT) Polyamine/Opine/Phosphonate Uptake Transporter (POPT) Quaternary Amine Uptake Transporter (QAT) Vitamin B12 Uptake Transporter (B12T) Iron Chelate Uptake Transporter (FeCT) Manganese/Zinc/Iron Chelate Uptake Transporter (MZT) Nitrate/Nitrite/Cyanate Uptake Transporter (NitT) Taurine Uptake Transporter (TauT) Cobalt Uptake Transporter (CoT) Thiamin Uptake Transporter (ThiT) Brachyspira Iron Transporter (BIT) Siderophore-Fe3+ Uptake Transporter (SIUT) Nickel Uptake Transporter (NiT) Nickel/Cobalt Uptake Transporter (NiCoT) Methionine Uptake Transporter (MUT) Lipid Exporter (LipidE)
Exporters Capsular Polysaccharide Exporter (CPSE) Lipooligosaccharide Exporter (LOSE) Lipopolysaccharide Exporter (LPSE) Teichoic Acid Exporter (TAE) Drug Exporter-1 (DrugE1) Lipid Exporter (LipidE) Putative Heme Exporter (HemeE) -Glucan Exporter (GlucanE) Protein-1 Exporter (Prot1E) Protein-2 Exporter (Prot2E) Peptide-1 Exporter (Pep1E) Peptide-2 Exporter (Pep2E) Peptide-3 Exporter (Pep3E) Probable Glycolipid Exporter (DevE) Na+ Exporter (NatE)
ATP-binding cassette transporter Microcin J25 Exporter (McjD) Drug/Siderophore Exporter-3 (DrugE3) (Putative) Drug Resistance ATPase-1 (Drug RA1) (Putative) Drug Resistance ATPase-2 (Drug RA2) Macrolide Exporter (MacB) Peptide-4 Exporter (Pep4E) 3-component Peptide-5 Exporter (Pep5E) Lipoprotein Translocase (LPT) -Exotoxin I Exporter (ETE) AmfS Peptide Exporter (AmfS-E) SkfA Peptide Exporter (SkfA-E) CydDC Cysteine and glutathione Exporter (CydDC-E)
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[92]
Images
Many structures of water-soluble domains of ABC proteins have been produced in recent years.[14]
More Readings
The ABC Transporters of Human Physiology and Disease (WSPC 2011) ISBN 978-981-4280-06-8 [93].
References
[1] http:/ / www. pdbe. org/ 1l7v [2] http:/ / pfam. sanger. ac. uk/ family?acc=PF00005 [3] http:/ / www. ebi. ac. uk/ interpro/ DisplayIproEntry?ac=IPR003439 [4] http:/ / www. expasy. org/ cgi-bin/ prosite-search-ac?PDOC00185 [5] http:/ / scop. mrc-lmb. cam. ac. uk/ scop/ search. cgi?tlev=fa;& amp;pdb=1b0u [6] http:/ / supfam. org/ SUPERFAMILY/ cgi-bin/ search. cgi?search_field=1b0u [7] http:/ / www. tcdb. org/ search/ result. php?tc=3. A. 1 [8] http:/ / opm. phar. umich. edu/ families. php?superfamily=17 [9] http:/ / opm. phar. umich. edu/ protein. php?search=3g5u [10] http:/ / pfam. sanger. ac. uk/ family/ PF00005?tab=pdbBlock [11] http:/ / www. rcsb. org/ pdb/ search/ smartSubquery. do?smartSearchSubtype=PfamIdQuery& pfamID=PF00005 [12] http:/ / www. ebi. ac. uk/ pdbe-srv/ PDBeXplore/ pfam/ ?pfam=PF00005 [13] http:/ / www. ebi. ac. uk/ thornton-srv/ databases/ cgi-bin/ pdbsum/ GetPfamStr. pl?pfam_id=PF00005 [14] Jones PM, George AM (Mar 2004). "The ABC transporter structure and mechanism: perspectives on recent research". Cell Mol Life Sci. 61 (6): 68299. doi:10.1007/s00018-003-3336-9. PMID15052411. [15] Ponte-Sucre, A (editor) (2009). ABC Transporters in Microorganisms. Caister Academic Press. ISBN978-1-904455-49-3. [16] Davidson A.L., Dassa E., Orelle C., Chen J. (2008). "Structure, function, and evolution of bacterial ATP-binding cassette systems". Microbiol. Mol. Biol. Rev. 72 (2): 317364. doi:10.1128/MMBR.00031-07. PMC2415747. PMID18535149. [17] Goffeau, A.; B. de Hertogh; and P.V. Baret. 2004. ABC Transporters. In: Encyclopedia of Biological Chemistry. Vol. 1, 1-5. [18] Henderson D.P., Payne S.M. (1994). "Vibrio cholerae iron transport system: roles of heme and siderophore iron transport in virulence and identification of a gene associated with multiple iron transport systems". Infect. Immun 62 (11): 51205. PMC303233. PMID7927795. [19] Cangelosi G.A., Ankenbauer R.G., Nester E.W. (1990). "Sugars induce the Agrobacterium virulence genes through a periplasmic binding protein and a transmembrane signal protein". Proc. Natl. Acad. Sci. USA 87 (17): 670812. doi:10.1073/pnas.87.17.6708. PMC54606. PMID2118656. [20] Kemner J.M., Liang X., Nester E.W. (1997). "The Agrobacterium tumefaciens virulence gene chvE is part of a putative ABC-type sugar transport operon". J. Bacteriol 179 (7): 24528. PMC178989. PMID9079938. [21] Poolman B., Spitzer J.J., Wood J.M. (2004). "Bacterial osmosensing: roles of membrane structure and electrostatics in lipid-protein and protein-protein interactions". Biochim. Biophys. Acta 1666 (12): 88104. doi:10.1016/j.bbamem.2004.06.013. PMID15519310. [22] Davidson A.L., Chen J. (2004). "ATP-binding cassette transporters in bacteria". Annu. Rev. Biochem 73: 241268. doi:10.1146/annurev.biochem.73.011303.073626. PMID15189142.
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External links
Szentptery Z, Kern A, Liliom K, Sarkadi B, Vradi A, Bakos E (Oct 2004). "The role of the conserved glycines of ATP-binding cassette signature motifs of MRP1 in the communication between the substrate-binding site and the catalytic centers" (http://www.jbc.org/cgi/content/full/279/40/41670). J Biol Chem. 279 (40): 416708. doi:10.1074/jbc.M406484200. PMID15252017. Fitzgerald ML, Okuhira K, Short GF, Manning JJ, Bell SA, Freeman MW (Nov 2004). "ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities". J Biol Chem. 279 (46): 4847785. doi:10.1074/jbc.M409848200. PMID15347662. Classification of ABC transporters (http://www.tcdb.org/tcdb/index.php?tc=3.A.1) in TCDB ABCdb (http://www-abcdb.biotoul.fr) Archaeal and Bacterial ABC Systems database, ABCdb ATP-Binding+cassette+transporters (http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=& term=ATP-Binding+cassette+transporters) at the US National Library of Medicine Medical Subject Headings (MeSH)
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