Atpbinding cassette transporters abc transporters utilize the energy of atp hydrolysis to translocate an unusually diverse set of substrates across cellular membranes. The energycoupling factor ecf transporters constitute a novel family of conserved membrane transporters in prokaryotes that have a similar domain organization to the atp binding cassette. Deficiencies of individual atpbinding cassettes have been associated with clinical diseases in a number of different organ systems. The role of atpbinding cassette transporters in bacterial. Structural biochemistrymembrane proteinsatpbinding. These proteins are fundamental to membrane transport of. Chapter 8 the atpbinding cassette transporter abca4. Moleculardynamics simulations of the atpapo state of a multidrug. Atpbinding cassette abc transporters couple atp hydrolysis to the uptake and efflux of solutes across the cell membrane in bacteria and eukaryotic cells. Inside the cell, the transporter recruits two molecules of atp for energy as the solute is. The atp binding cassette transporter a1 abca1 mediates cholesterol efflux from hepatocytes to extracellular apolipoprotein a1 and moves cholesterol within cell membranes.
Information and translations of atpbinding cassette transporters in the most comprehensive dictionary definitions resource on the web. Feb 05, 2015 in this video we discuss the structure and function of atp binding cassette transporters. Atpbinding cassette abc transporter associated with antigen processing 1 tap1 nucleotidebinding domain the harvard community has made this article openly available. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. A member of a ubiquitous superfamily of membranebound pumps present in all prokaryotes, fungi, plants, yeast and animals. Among them, a polymorphism in the abc transporter gene atpbinding cassette transporter isoform g2 has been highlighted. Overexpression of certain abc transporters occurs in cancer cell lines and tumors that are multidrug resistant. Thus, there are two atp binding sites lying at the interface between the two nbd subunits. The energycoupling factor ecf transporters constitute a novel family of conserved membrane transporters in prokaryotes that have a similar domain organization to the atpbinding cassette.
In insects, abc transporters are of special interest because of their role in insecticide resistance. Individual subunits are typically made up of two groups of 6tmspanning domains, with two nucleotide binding domains nbd. Atp binding cassette transporters, also known as abc transporters, are transmembrane proteins that utilize the energy of atp hydrolysis to carry out certain biological processes including translocation of various substrates across membranes and nontransportrelated processes such as translation of rna and dna repair. Identification of sterolindependent regulatory elements in the human atpbinding cassette transporter a1 abca1 promoter. The conformational transition pathways of atpbinding cassette transporter btucd revealed by targeted molecular dynamics simulation jingwei weng, kangnian fan, wenning wang shanghai key laboratory of molecular catalysis and innovative materials, department of chemistry and institute of biomedical sciences, fudan university, shanghai. Many abc transporters such as pglycoprotein pgp, multidrug resistanceassociated protein 1 mrp1 and breast cancer resistance protein bcrp are highly expressed in bronchial epithelium. Jan, 2012 the atp binding cassette transporter superfamily is present in all three domains of life. The program hingefinder was used to analyze domain rotations using. The role of atpbinding cassette transporters in bacterial pathogenicity. Nebert2 1molecular toxicology and environmental health sciences program, department of pharmaceutical sciences, university of colorado denver, aurora, co 80045, usa 2department of environmental health and center for environmental genetics ceg, university. In bacteria, these transporters are important virulence factors because they play roles in nutrient uptake and in secretion of toxins and antimicrobial agents.
Definition of atpbinding cassette transporters in the dictionary. Atpbinding cassette transporter of arabidopsis, has been identified by contrasting cd tolerance in tdna insertion mutant and the overexpressing plant kim et al. In fact, a gene encoding putative gshcd complex excluder of the mitochondria, which is an yeast hmt1 homologue in arabidopsis atatm3. Vasilis vasiliou, konstandinos vasiliou, and daniel w nebert. A plant plasma membrane atp binding cassettetype transporter. They transport a wide variety of substrates across extra. The atp binding cassette transporter superfamily is present in all three domains of life. Lmra is an atp binding cassette abc multidrug transporter in lactococcus lactis that is a structural and functional homologue of the human multidrug resistance pglycoprotein mdr1 abcb1. The btucd model shows that a single nbd does not constitute an independent functional structure by itself, but that both nbds interact, with the abc signature of one nbd interacting with the other motifs from the other nbd to constitute an atp binding site. Human atpbinding cassette abc transporter family vasilis vasiliou,1 konstandinos vasiliou1 and daniel w. The atpbinding cassette abc transporter superfamily contains membrane proteins that translocate a wide variety of substrates across extra and intracellular membranes, including metabolic products, lipids and sterols, and drugs. The conformational transition pathways of atpbinding.
Atpbinding cassette abc transporters constitute one of the largest. The atpbinding cassette transporters abc transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene. The atpbinding cassette abc superfamily is the largest family of transporters in living organisms, ranging from bacteria to humans 810. Antibodies for proteins involved in atpbinding cassette abc transporter pathways, according to their panthergene ontology classification. Apr 14, 20 the energycoupling factor ecf transporters constitute a novel family of conserved membrane transporters in prokaryotes that have a similar domain organization to the atp binding cassette. The atpbinding cassette transporter superfamily is present in all three domains of life. This ubiquitous class of integral membrane proteins have diverse biological functions, but their fundamental role involves the unidirectional translocation of compounds across cellular membranes in an atp coupled process. Integral membrane atp binding cassette abc transporters are ubiquitous in all three domains of life and form one of the largest classes of membrane proteins 1,2. Inhibition of lipid efflux by glybenclamide treatment or by mutation of the atpbinding cassette of abca1 showed a close correlation between lipid efflux, the binding of apoai to cells, and crosslinking of apoai to abca1. Abcg2 elisa kit human atpbinding cassette transporter g2 elisa. Dhelix influences dimerization of the atpbinding cassette. Through the hydrolysis of atp to generate energy, abc transporters move a wide variety of substrates across membranes, including ions, sugars, amino acids, polypeptides, toxic metabolites, xenobiotics, and even drugs and toxins. Langmann t, porschozcurumez m, heimerl s, et al identification of sterolindependent regulatory elements in the human atp binding cassette transporter a1 abca1 promoter. A system that takes in a particular nutrient or solute uses a solute binding protein to grab the solute.
Arabidopsis pen3pdr8, an atp binding cassette transporter. Atp binding cassette abc transporters atp binding cassette abc transporters are a large superfamily of membrane proteins with varying functions 5,6. The atpbinding cassette transporter a1 abca1 mediates cholesterol efflux from hepatocytes to extracellular apolipoprotein a1 and moves cholesterol within cell membranes. The role of atp binding cassette transporter genes in the progression of prostate cancer. Thus, the correct gene name for bl is abcbi, for b4 is abcb4, and so forth. Atpbinding cassette transporter a1 abca1 functions as a cholesterol efflux regulatory protein. The abcc2 gene provides instructions for producing a protein called multidrug resistance protein 2 mrp2. Furthermore, it generates highdensity lipoprotein hdl particles. The atp binding cassette transporters abc transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. The human breast cancer resistance protein is an atpbinding cassette abc multidrug transporter that affects the bioavailability of chemotherapeutic drugs and can confer drug resistance on cancer cells. Clustering dendrogram of the human atpbinding cassette abc transporter genes.
Plant atp binding cassette abc transporters are membrane proteins that are important for transporting a wide range of compounds, including secondary. Atpbinding cassette abc transporters part 1 youtube. Atppowered pumps include the atpbinding cassette abc pumps. Atp binding cassette abc transporter associated with antigen processing 1 tap1 nucleotide binding domain the harvard community has made this article openly available. Atpbinding cassette abc transporters in atherosclerosis. Atpbinding cassette abc transporter antibodies invitrogen. It is the second member of the abcg subfamily, other members of which are associated with human steroid disorders such as hypercholesterolemia. Atpbinding cassette abc transporters in normal and. Many abc transporters such as pglycoprotein pgp, multidrug resistanceassociated protein 1 mrp1 and breast cancer resistance protein bcrp are highly expressed. Arabidopsis pen3pdr8, an atp binding cassette transporter, contributes to nonhost resistance to inappropriate pathogens that enter by direct penetration w oa mo.
Atp binding cassette transporter abca1 member 1 of human transporter subfamily abca, also known as the cholesterol efflux regulatory protein cerp is a protein which in humans is encoded by the abca1 gene. Atpbinding cassette abc transporters part 3 duration. Atpbinding cassette how is atpbinding cassette abbreviated. Upregulation of the atpbinding cassette transporter a1. Tracing the structural evolution of eukaryotic atp binding.
Human atpbinding cassette abc transporter family human. Atpbinding cassette abc3 transporters are an ancient protein family. Individual subunits are typically made up of two groups of 6tmspanning domains, with two nucleotidebinding domains nbd. Flexibletorigid transition is central for substrate transport in the. Atpbinding cassette abc transporters atpbinding cassette abc transporters are a large superfamily of membrane proteins with varying functions 5,6. This process involves binding of apoai to the cell surface and phospholipid translocation by abca1. Besides abca1, expression of macrophage atpbinding cassette transporter g1 abcg1 is intimately linked to cellular cholesterol content, suggesting its potential role in cholesterol transport and homeostasis. Atpbinding cassette abc transporter pglycoprotein mdr1abcb1 or the breast cancer resistance protein. Abcg1 is a half transporter that needs to form homodimer or heterodimer to be functional. The atp binding cassette multidrug transporter lmra and lipid. Atpbinding cassette transporter abca1 member 1 of human transporter subfamily abca, also known as the cholesterol efflux regulatory protein cerp is a protein which in humans is encoded by the abca1 gene. Atp binding cassette transporters are ubiquitous membrane proteins characterized by active atp dependent movement of a range of substrates, including ions, lipids, peptides, steroids. The importance of this class of proteins in eukaryotic systems is well established. Lmra is also homologous to msba, an essential abc transporter in escherichia coli involved in the trafficking of lipids, including lipid a.
Theodoulou crop performance and improvement division, rothamsted research, harpenden, hertfordshire al5 2jq. These pumps use energy released by atp hydrolysis to move substrates across membranes in or out of cells or into cellular vesicles, against their electrochemical gradient. Atpbinding cassette transporters are ubiquitous membrane proteins characterized by active atpdependent movement of a range of substrates, including ions, lipids, peptides, steroids. Its members exist in species from all kingdoms of life, where they play important, frequently essential roles 1, 2. The mrna expression level of adenosine triphosphate binding cassette abc transporter family, i. Atp binding cassette transporter of arabidopsis, has been identified by contrasting cd tolerance in tdna insertion mutant and the overexpressing plant kim et al. Human atpbinding cassette abc transporter family ncbi nih. Atpbinding cassette transporters in bacteria annual. The conformational transition pathways of atpbinding cassette. They have evolved to transport a variety of substrates.
An abc transporter typically consist of two hydrophobic proteins that form a membrane channel and two peripheral cytoplasmic proteins with nucleotide binding domains for binding to atp. The atp binding cassette transporter proteins are essential for normal transport of compounds in numerous biologic systems mulugeta et al. The comatose atpbinding cassette transporter is required for full fertility in arabidopsis1woa steven footitt2, daniela dietrich, aaron fait, alisdair r. Abc pumps constitute a large, diverse and ubiquitous superfamily. Atpbinding cassette abc transporters in human metabolism. Molecular cloning and expression profile of an atpbinding. Abc transporters belong to the atpbinding cassette superfamily, which uses the hydrolysis of atp to translocate a variety of compounds across biological membranes. Atpbinding cassette transporter family transporters. The conformational transition pathways of atp binding cassette transporter btucd revealed by targeted molecular dynamics simulation jingwei weng, kangnian fan, wenning wang shanghai key laboratory of molecular catalysis and innovative materials, department of chemistry and institute of biomedical sciences, fudan university, shanghai.
Atpbinding cassette abc transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energydependent manner. In this video we discuss the structure and function of atpbinding cassette transporters. Atp binding cassette transporter abca7 regulates nkt cell development and function by controlling cd1d expression and lipid raft content the harvard community has made this article openly available. Atp binding cassette abc transporter pglycoprotein. Tgd1, 2, and 3 proteins involved in lipid trafficking.
The atp binding cassette multidrug transporter lmra and. You 1 1hubei key laboratory of food crop germplasm and genetic improvement. The role of atpbinding cassette transporter genes in the. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Atp binding cassette sub family a member 1 atp binding cassette transporter 1 or abc 1 or atp binding cassette 1 or cholesterol efflux regulatory. A functional steroidbinding element in an atpbinding. Atp binding cassette abc solute carrier slc transporters. The atp binding cassette abc superfamily of membrane transporters is found in all prokaryotic and eukaryotic species. Atpbinding cassette transporters use the energy of atp hydrolysis to. Atpbinding cassette transporters, also known as abc transporters, are transmembrane proteins that utilize the energy of atp hydrolysis to carry out certain biological processes including translocation of various substrates across membranes and nontransportrelated processes such as translation of rna and dna repair. Atpbindingcassette abc transporters are molecular pumps that translocate. This protein is one of a family of multidrug resistance proteins involved in the transport of substances out of cells.
Atpbinding cassette abc transporters part 2 youtube. It is represented in all extant phyla, from prokaryotes to humans. Structure of a bacterial energycoupling factor transporter. Jan 16, 20 the atp binding cassette abc transporters belong to a large superfamily of proteins that have important physiological functions in all living organisms. Abc transporter lipid metabolism cholesterol mutation introduction the atpbinding cassette abc superfamily of active transporters is composed of about 50 functionally diverse prokaryotic and eukaryotic transmembrane proteins higgins 1992, michaelis and berkower 1995. Deficiencies of individual atp binding cassettes have been associated with clinical diseases in a number of different organ systems. In a third phase, glutathione and pcscd complexes are excluded from the cytosol into vacuolar or extracellular compartments by various transporters, among which are abc transporters 6, 7. The atpbinding cassette abc transporters belong to a large superfamily of proteins that have important physiological functions in all living organisms. Signal peptide was analyzed by the online software signalp 4. For example, mrp2 clears certain drugs from organs and tissues, playing a part in drug metabolism. Atp binding cassette transporters abc transporters utilize the energy of atp hydrolysis to translocate an unusually diverse set of substrates across cellular membranes.
Btucd is a member of the atpbinding cassette transporters in escherichia coli that. Abca1, an atp binding cassette transporter mutated in tangier disease, promotes cellular phospholipid and cholesterol efflux by loading free apoai with these lipids. Atp binding cassette transporter abca7 regulates nkt cell. The root abc is omitted from the figure to simplify it. Abca1 abca subfamily iupharbps guide to pharmacology. Atpbinding cassette or abc transporters form a large and ubiquitous superfamily of transporters that participate in a wide range of physiological processes. Nebert2 1molecular toxicology and environmental health sciences program, department of pharmaceutical sciences, university of colorado. Plants free fulltext tomato atpbinding cassette transporter. The role of atpbinding cassette transporter genes in the progression of prostate cancer. It is represented in all extant phyla, from prokaryotes to humans abc transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membraneassociated aaa atpases. The role of atp binding cassette transporters in bacterial pathogenicity. An animation was then made in which the opposite nbd monomer was static. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Structure, function, and gene family comparison between rice and arabidopsis. Atmrp6 atabcc6, an atpbinding cassette transporter. They utilize the energy obtained from atp hydrolysis for import and export of substrates across the into transbilayer. Functional analysis of the atpbinding cassette abc. The human atpbinding cassette abc transporter superfamily. Hdl protects against arteriosclerosis and cardiovascular disease. The atpbinding cassette transporter proteins are essential for normal transport of compounds in numerous biologic systems mulugeta et al. The atp binding cassette abc superfamily of membrane transporters is found in all prokaryotic and eukaryotic spe cies. Molecular cloning and expression profile of an atpbinding cassette abc transporter gene from the hemipteran insect nilaparvata lugens w. Atpbinding cassette transporter isoform g2 was found to be involved in renal urate elimination, and the presence of the q141k polymorphism to induce a 2fold decrease in urate efflux. In silico genomewide analysis of the atpbinding cassette.
All members of this family are involved in the active transport of many chemically and structurally unrelated compounds and use atp hydrolysis as a source of energy higgins, 1992. Abc transporters belong to the atp binding cassette superfamily, which uses the hydrolysis of atp to translocate a variety of compounds across biological membranes. Most are integral membrane proteins that transport a broad spectrum of substrates across lipid membranes. Abca4, also known as abcr, is a 250 kda singlechain abc transporter localized to the disk margins of vertebrate photoreceptor outer segments. The comatose atp binding cassette transporter is required for full fertility in arabidopsis1woa steven footitt2, daniela dietrich, aaron fait, alisdair r. Abc transporters are minimally constituted of two conserved regions. Human atp binding cassette abc transporter family vasilis vasiliou,1 konstandinos vasiliou1 and daniel w. Atpbinding cassette transporter a1 abca1 functions as a.