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      Diversity in ABC transporters: Type I, II and III importers

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          Abstract

          ATP-binding cassette transporters are multi-subunit membrane pumps that transport substrates across membranes. While significant in the transport process, transporter architecture exhibits a range of diversity that we are only beginning to recognize. This divergence may provide insight into the mechanisms of substrate transport and homeostasis. Until recently, ABC importers have been classified into two types, but with the emergence of energy-coupling factor (ECF) transporters there are potentially three types of ABC importers. In this review, we summarize an expansive body of research on the three types of importers with an emphasis on the basics that underlie ABC importers, such as structure, subunit composition and mechanism.

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          Most cited references91

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          Bacterial iron homeostasis.

          Iron is essential to virtually all organisms, but poses problems of toxicity and poor solubility. Bacteria have evolved various mechanisms to counter the problems imposed by their iron dependence, allowing them to achieve effective iron homeostasis under a range of iron regimes. Highly efficient iron acquisition systems are used to scavenge iron from the environment under iron-restricted conditions. In many cases, this involves the secretion and internalisation of extracellular ferric chelators called siderophores. Ferrous iron can also be directly imported by the G protein-like transporter, FeoB. For pathogens, host-iron complexes (transferrin, lactoferrin, haem, haemoglobin) are directly used as iron sources. Bacterial iron storage proteins (ferritin, bacterioferritin) provide intracellular iron reserves for use when external supplies are restricted, and iron detoxification proteins (Dps) are employed to protect the chromosome from iron-induced free radical damage. There is evidence that bacteria control their iron requirements in response to iron availability by down-regulating the expression of iron proteins during iron-restricted growth. And finally, the expression of the iron homeostatic machinery is subject to iron-dependent global control ensuring that iron acquisition, storage and consumption are geared to iron availability and that intracellular levels of free iron do not reach toxic levels.
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            Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.

            The alpha- and beta-subunits of membrane-bound ATP synthase complex bind ATP and ADP: beta contributes to catalytic sites, and alpha may be involved in regulation of ATP synthase activity. The sequences of beta-subunits are highly conserved in Escherichia coli and bovine mitochondria. Also alpha and beta are weakly homologous to each other throughout most of their amino acid sequences, suggesting that they have common functions in catalysis. Related sequences in both alpha and beta and in other enzymes that bind ATP or ADP in catalysis, notably myosin, phosphofructokinase, and adenylate kinase, help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.
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              ABC transporters in cancer: more than just drug efflux pumps.

              Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. However, a considerable body of evidence also points to their importance in cancer extending beyond drug transport to fundamental roles in tumour biology. Currently, much of the evidence for these additional roles is correlative and definitive studies are needed to confirm causality. We propose that delineating the precise roles of these transporters in tumorigenesis and treatment response will be important for the development of more effective targeted therapies.
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                Author and article information

                Journal
                Crit Rev Biochem Mol Biol
                Crit. Rev. Biochem. Mol. Biol
                BMG
                Critical Reviews in Biochemistry and Molecular Biology
                Informa Healthcare USA, Inc.
                1040-9238
                1549-7798
                October 2014
                26 August 2014
                : 49
                : 5
                : 426-437
                Affiliations
                Department of Molecular Biosciences, Northwestern University Evanston, ILUSA
                Author notes
                Address for correspondence: Heather W. Pinkett, Department of Molecular Biosciences, Northwestern University Evanston, IL 60208USA. Tel: +1 847 467-4048. E-mail: h-pinkett@ 123456northwestern.edu
                Article
                10.3109/10409238.2014.953626
                4245157
                25155087
                56526440-ba82-4ad6-9bdc-a6e034b6955c
                © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted

                This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.

                History
                : 2 June 2014
                : 25 July 2014
                : 7 August 2014
                Categories
                Review Article

                Molecular biology
                abc transporters,accessory domain,ecf,importers,micronutrient and metal transport,nucleotide binding domain,regulatory domain,type i,type ii,type iii

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