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ABC Transporter

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Kaspar P Locher – 1st expert on this subject based on the ideXlab platform

  • structural basis of trans inhibition in a molybdate tungstate ABC Transporter
    Science, 2008
    Co-Authors: Sabina Gerber, Mireia Comellasbigler, Birke A Goetz, Kaspar P Locher


    Transport across cellular membranes is an essential process that is catalyzed by diverse membrane transport proteins. The turnover rates of certain Transporters are inhibited by their substrates in a process termed trans-inhibition, whose structural basis is poorly understood. We present the crystal structure of a molybdate/tungstate ABC Transporter (ModBC) from Methanosarcina acetivorans in a trans-inhibited state. The regulatory domains of the nucleotide-binding subunits are in close contact and provide two oxyanion binding pockets at the shared interface. By specifically binding to these pockets, molybdate or tungstate prevent adenosine triphosphatase activity and lock the Transporter in an inward-facing conformation, with the catalytic motifs of the nucleotide-binding domains separated. This allosteric effect prevents the Transporter from switching between the inward-facing and the outward-facing states, thus interfering with the alternating access and release mechanism.

  • asymmetry in the structure of the ABC Transporter binding protein complex btucd btuf
    Science, 2007
    Co-Authors: Rikki N Hvorup, Birke A Goetz, Martina Niederer, Kaspar Hollenstein, Eduardo Perozo, Kaspar P Locher


    BtuCD is an adenosine triphosphate–binding cassette (ABC) Transporter that translocates vitamin B 12 from the periplasmic binding protein BtuF into the cytoplasm of Escherichia coli. The 2.6 angstrom crystal structure of a complex BtuCD-F reveals substantial conformational changes as compared with the previously reported structures of BtuCD and BtuF. The lobes of BtuF are spread apart, and B 12 is displaced from the binding pocket. The transmembrane BtuC subunits reveal two distinct conformations, and the translocation pathway is closed to both sides of the membrane. Electron paramagnetic resonance spectra of spin-labeled cysteine mutants reconstituted in proteoliposomes are consistent with the conformation of BtuCD-F that was observed in the crystal structure. A comparison with BtuCD and the homologous HI1470/71 protein suggests that the structure of BtuCD-F may reflect a posttranslocation intermediate.

  • structure of an ABC Transporter in complex with its binding protein
    Nature, 2007
    Co-Authors: Kaspar Hollenstein, Dominik C Frei, Kaspar P Locher


    The structure of a putative molybdate Transporter (ModB2C2) is presented in complex with its cognate binding protein ModA. These results help provide the structural basis for the ATP-driven transport mechanism of both clinically relevant multi-drug ABC exporters and of ABC importers facilitating bacterial nutrient uptake. ATP-binding cassette (ABC) Transporter proteins carry diverse substrates across cell membranes1. Whereas clinically relevant ABC exporters are implicated in various diseases or cause multidrug resistance of cancer cells2,3, bacterial ABC importers are essential for the uptake of nutrients4, including rare elements such as molybdenum. A detailed understanding of their mechanisms requires direct visualization at high resolution and in distinct conformations. Our recent structure of the multidrug ABC exporter Sav1866 has revealed an outward-facing conformation of the transmembrane domains coupled to a closed conformation of the nucleotide-binding domains, reflecting the ATP-bound state5. Here we present the 3.1 A crystal structure of a putative molybdate Transporter (ModB2C2) from Archaeoglobus fulgidus in complex with its binding protein (ModA). Twelve transmembrane helices of the ModB subunits provide an inward-facing conformation, with a closed gate near the external membrane boundary. The ATP-hydrolysing ModC subunits reveal a nucleotide-free, open conformation, whereas the attached binding protein aligns the substrate-binding cleft with the entrance to the presumed translocation pathway. Structural comparison of ModB2C2A with Sav1866 suggests a common alternating access and release mechanism, with binding of ATP promoting an outward-facing conformation and dissociation of the hydrolysis products promoting an inward-facing conformation.

Chris Whitfield – 2nd expert on this subject based on the ideXlab platform

  • periplasmic depolymerase provides insight into ABC Transporter dependent secretion of bacterial capsular polysaccharides
    Proceedings of the National Academy of Sciences of the United States of America, 2018
    Co-Authors: Sean D Liston, S A Mcmahon, Michael D Suits, James H Naismith, Chris Whitfield


    Capsules are surface layers of hydrated capsular polysaccharides (CPSs) produced by many bacteria. The human pathogen Salmonella enterica serovar Typhi produces “Vi antigen” CPS, which contributes to virulence. In a conserved strategy used by bacteria with diverse CPS structures, translocation of Vi antigen to the cell surface is driven by an ATP-binding cassette (ABC) Transporter. These Transporters are engaged in heterooligomeric complexes proposed to form an enclosed translocation conduit to the cell surface, allowing the Transporter to power the entire process. We identified Vi antigen biosynthesis genetic loci in genera of the Burkholderiales , which are paradoxically distinguished from S. Typhi by encoding VexL, a predicted pectate lyase homolog. Biochemical analyses demonstrated that VexL is an unusual metal-independent endolyase with an acidic pH optimum that is specific for O-acetylated Vi antigen. A 1.22-A crystal structure of the VexL-Vi antigen complex revealed features which distinguish common secreted catabolic pectate lyases from periplasmic VexL, which participates in cell-surface assembly. VexL possesses a right-handed parallel β-superhelix, of which one face forms an electropositive glycan-binding groove with an extensive hydrogen bonding network that includes Vi antigen acetyl groups and confers substrate specificity. VexL provided a probe to interrogate conserved features of the ABC Transporter-dependent export model. When introduced into S . Typhi, VexL localized to the periplasm and degraded Vi antigen. In contrast, a cytosolic derivative had no effect unless export was disrupted. These data provide evidence that CPS assembled in ABC Transporter-dependent systems is actually exposed to the periplasm during envelope translocation.

  • architecture of a channel forming o antigen polysaccharide ABC Transporter
    Nature, 2018
    Co-Authors: Yunchen Bi, Chris Whitfield, Evan Mann, Jochen Zimmer


    The crystal structure of a channel-forming O-antigen polysaccharide ABC Transporter suggests a novel biopolymer translocation mechanism. Bacterial cells are decorated with polysaccharides such as O-antigens, which help them to evade the innate immune responses of the host. In Gram-negative bacteria, these polysaccharides are transported from the cytoplasm to the periplasm before being incorporated into the outer membrane. In this paper, Jochen Zimmer and colleagues report the crystal structure of a bacterial O-antigen polysaccharide Transporter. This represents a key structure in bacterial cell envelope biogenesis. Unusually for ATP-binding cassette (ABC) Transporters, which usually operate by an alternating access model, the O-antigen Transporter in its open state forms a continuous channel which spans the entire membrane. As a result, the authors suggest that the polysaccharides are transported via a processive mechanism whereby they thread through the open channel. O-antigens are cell surface polysaccharides of many Gram-negative pathogens that aid in escaping innate immune responses1. A widespread O-antigen biosynthesis mechanism involves the synthesis of the lipid-anchored polymer on the cytosolic face of the inner membrane, followed by transport to the periplasmic side where it is ligated to the lipid A core to complete a lipopolysaccharide molecule2. In this pathway, transport to the periplasm is mediated by an ATP-binding cassette (ABC) Transporter, called Wzm–Wzt. Here we present the crystal structure of the Wzm–Wzt homologue from Aquifex aeolicus in an open conformation. The Transporter forms a transmembrane channel that is sufficiently wide to accommodate a linear polysaccharide. Its nucleotide-binding domain and a periplasmic extension form ‘gate helices’ at the cytosolic and periplasmic membrane interfaces that probably serve as substrate entry and exit points. Site-directed mutagenesis of the gates impairs in vivo O-antigen secretion in the Escherichia coli prototype. Combined with a closed structure of the isolated nucleotide-binding domains, our structural and functional analyses suggest a processive O-antigen translocation mechanism, which stands in contrast to the classical alternating access mechanism of ABC Transporters.

  • structure biosynthesis and function of bacterial capsular polysaccharides synthesized by ABC Transporter dependent pathways
    Carbohydrate Research, 2013
    Co-Authors: Lisa M Willis, Chris Whitfield


    Bacterial capsules are formed primarily from long-chain polysaccharides with repeat-unit structures. A given bacterial species can produce a range of capsular polysaccharides (CPSs) with different structures and these help distinguish isolates by serotyping, as is the case with Escherichia coli K antigens. Capsules are important virulence factors for many pathogens and this review focuses on CPSs synthesized via ATP-binding cassette (ABC) Transporter-dependent processes in Gram-negative bacteria. Bacteria utilizing this pathway are often associated with urinary tract infections, septicemia, and meningitis, and E. coli and Neisseria meningitidis provide well-studied examples. CPSs from ABC Transporter-dependent pathways are synthesized at the cytoplasmic face of the inner membrane through the concerted action of glycosyltransferases before being exported across the inner membrane and translocated to the cell surface. A hallmark of these CPSs is a conserved reducing terminal glycolipid composed of phosphatidylglycerol and a poly-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) linker. Recent discovery of the structure of this conserved lipid terminus provides new insights into the early steps in CPS biosynthesis.

Enrico Martinoia – 3rd expert on this subject based on the ideXlab platform

  • a rice ABC Transporter osABCc1 reduces arsenic accumulation in the grain
    Proceedings of the National Academy of Sciences of the United States of America, 2014
    Co-Authors: Won Yong Song, Enrico Martinoia, Naoki Yamaji, Tomohiro Yamaki, Donghwi Ko, Kihong Jung, Miho Fujiikashino, Gynheung An


    Arsenic (As) is a chronic poison that causes severe skin lesions and cancer. Rice (Oryza sativa L.) is a major dietary source of As; therefore, reducing As accumulation in the rice grain and thereby diminishing the amount of As that enters the food chain is of critical importance. Here, we report that a member of the Oryza sativa C-type ATP-binding cassette (ABC) Transporter (OsABCC) family, OsABCC1, is involved in the detoxification and reduction of As in rice grains. We found that OsABCC1 was expressed in many organs, including the roots, leaves, nodes, peduncle, and rachis. Expression was not affected when plants were exposed to low levels of As but was up-regulated in response to high levels of As. In both the basal nodes and upper nodes, which are connected to the panicle, OsABCC1 was localized to the phloem region of vascular bundles. Furthermore, OsABCC1 was localized to the tonoplast and conferred phytochelatin-dependent As resistance in yeast. Knockout of OsABCC1 in rice resulted in decreased tolerance to As, but did not affect cadmium toxicity. At the reproductive growth stage, the As content was higher in the nodes and in other tissues of wild-type rice than in those of OsABCC1 knockout mutants, but was significantly lower in the grain. Taken together, our results indicate that OsABCC1 limits As transport to the grains by sequestering As in the vacuoles of the phloem companion cells of the nodes in rice.

  • pdr type ABC Transporter mediates cellular uptake of the phytohormone abscisic acid
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Joohyun Kang, Jaeung Hwang, Sarah M Assmann, Enrico Martinoia


    Abscisic acid (ABA) is a ubiquitous phytohormone involved in many developmental processes and stress responses of plants. ABA moves within the plant, and intracellular receptors for ABA have been recently identified; however, no ABA Transporter has been described to date. Here, we report the identification of the ATP-binding cassette (ABC) Transporter Arabidopsis thaliana Pleiotropic drug resistance Transporter PDR12 (AtPDR12)/ABCG40 as a plasma membrane ABA uptake Transporter. Uptake of ABA into yeast and BY2 cells expressing AtABCG40 was increased, whereas ABA uptake into protoplasts of atABCg40 plants was decreased compared with control cells. In response to exogenous ABA, the up-regulation of ABA responsive genes was strongly delayed in atABCg40 plants, indicating that ABCG40 is necessary for timely responses to ABA. Stomata of loss-of-function atABCg40 mutants closed more slowly in response to ABA, resulting in reduced drought tolerance. Our results integrate ABA-dependent signaling and transport processes and open another avenue for the engineering of drought-tolerant plants.

  • an ABC Transporter mutation alters root exudation of phytochemicals that provoke an overhaul of natural soil microbiota
    Plant Physiology, 2009
    Co-Authors: Dayakar V Badri, Enrico Martinoia, Naira Quintana, Elie El G Kassis, Young Hae Choi, Akifumi Sugiyama, Robert Verpoorte, Daniel K Manter, Jorge M Vivanco


    Root exudates influence the surrounding soil microbial community, and recent evidence demonstrates the involvement of ATP-binding cassette (ABC) Transporters in root secretion of phytochemicals. In this study, we examined effects of seven Arabidopsis (Arabidopsis thaliana) ABC Transporter mutants on the microbial community in native soils. After two generations, only the Arabidopsis ABCg30 (Atpdr2) mutant had significantly altered both the fungal and bacterial communities compared with the wild type using automated ribosomal intergenic spacer analysis. Similarly, root exudate profiles differed between the mutants; however, the largest variance from the wild type (Columbia-0) was observed in ABCg30, which showed increased phenolics and decreased sugars. In support of this biochemical observation, whole-genome expression analyses of ABCg30 roots revealed that some genes involved in biosynthesis and transport of secondary metabolites were up-regulated, while some sugar Transporters were down-regulated compared with genome expression in wild-type roots. Microbial taxa associated with Columbia-0 and ABCg30 cultured soils determined by pyrosequencing revealed that exudates from ABCg30 cultivated a microbial community with a relatively greater abundance of potentially beneficial bacteria (i.e. plant-growth-promoting rhizobacteria and nitrogen fixers) and were specifically enriched in bacteria involved in heavy metal remediation. In summary, we report how a single gene mutation from a functional plant mutant influences the surrounding community of soil organisms, showing that genes are not only important for intrinsic plant physiology but also for the interactions with the surrounding community of organisms as well.