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A reciprocating twin-channel model for ABC transporters

Published online by Cambridge University Press:  30 April 2014

Peter M. Jones  and
Anthony M. George
Peter M. Jones*
Affiliation:
School of Medical and Molecular Biosciences, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia
Anthony M. George
Affiliation:
School of Medical and Molecular Biosciences, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia
*
*Author for Correspondence: Peter M. Jones, School of Medical and Molecular Biosciences, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia. Tel.: +612 9514 4158; Fax: +612 9514 8206; Email: Peter.Jones-2@uts.edu.au
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Abstract

ABC transporters comprise a large, diverse, and ubiquitous superfamily of membrane active transporters. Their core architecture is a dimer of dimers, comprising two transmembrane (TM) domains that bind substrate, and two ATP-binding cassettes, which use the cell's energy currency to couple substrate translocation to ATP hydrolysis. Despite the availability of over a dozen resolved structures and a wealth of biochemical and biophysical data, this field is bedeviled by controversy and long-standing mechanistic questions remain unresolved. The prevailing paradigm for the ABC transport mechanism is the Switch Model, in which the ATP-binding cassettes dimerize upon binding two ATP molecules, and thence dissociate upon sequential ATP hydrolysis. This cycle of nucleotide-binding domain (NBD) dimerization and dissociation is coupled to a switch between inward- or outward facing conformations of a single TM channel; this alternating access enables substrate binding on one face of the membrane and its release at the other. Notwithstanding widespread acceptance of the Switch Model, there is substantial evidence that the NBDs do not separate very much, if at all, and thus physical separation of the ATP cassettes observed in crystallographic structures may be an artefact. An alternative Constant Contact Model has been proposed, in which ATP hydrolysis occurs alternately at the two ATP-binding sites, with one of the sites remaining closed and containing occluded nucleotide at all times. In this model, the cassettes remain in contact and the active sites swing open in an alternately seesawing motion. Whilst the concept of NBD association/dissociation in the Switch Model is naturally compatible with a single alternating-access channel, the asymmetric functioning proposed by the Constant Contact model suggests an alternating or reciprocating function in the TMDs. Here, a new model for the function of ABC transporters is proposed in which the sequence of ATP binding, hydrolysis, and product release in each active site is directly coupled to the analogous sequence of substrate binding, translocation and release in one of two functionally separate substrate translocation pathways. Each translocation pathway functions 180° out of phase. A wide and diverse selection of data for both ABC importers and exporters is examined, and the ability of the Switch and Reciprocating Models to explain the data is compared and contrasted. This analysis shows that not only can the Reciprocating Model readily explain the data; it also suggests straightforward explanations for the function of a number of atypical ABC transporters. This study represents the most coherent and complete attempt at an all-encompassing scheme to explain how these important proteins work, one that is consistent with sound biochemical and biophysical evidence.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 47 , Issue 3 , August 2014 , pp. 189 - 220
Copyright
Copyright © Cambridge University Press 2014 

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References

5. References

Abuznait, A. H., Qosa, H., Busnena, B. A., EL Sayed, K. A. & Kaddoumi, A. (2013). Olive-oil-derived oleocanthal enhances beta-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: in vitro and in vivo studies. ACS Chemical Neuroscience 4(6), 973–982.Google Scholar
Aleksandrov, A. A., Kota, P., Aleksandrov, L. A., He, L., Jensen, T., Cui, L., Gentzsch, M., Dokholyan, N. V. & Riordan, J. R. (2010). Regulatory insertion removal restores maturation, stability and function of DeltaF508 CFTR. Journal of Molecular Biology 401(2), 194–210.Google Scholar
Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L. & Chang, G. (2009). Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323(5922), 1718–1722.Google Scholar
Allikmets, R., Shroyer, N. F., Singh, N., Seddon, J. M., Lewis, R. A., Bernstein, P. S., Peiffer, A., Zabriskie, N. A., Li, Y., Hutchinson, A., Dean, M., Lupski, J. R. & Leppert, M. (1997). Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 277(5333), 1805–1807.Google Scholar
Ames, G. F., Mimura, C. S., Holbrook, S. R. & Shyamala, V. (1992). Traffic ATPases: a superfamily of transport proteins operating from Escherichia coli to humans. Advances in Enzymology and Related Areas of Molecular Biology 65, 1–47.Google Scholar
Ames, G. F., Liu, C. E., Joshi, A. K. & Nikaido, K. (1996). Liganded and unliganded receptors interact with equal affinity with the membrane complex of periplasmic permeases, a subfamily of traffic ATPases. Journal of Biological Chemistry 271(24), 14264–14270.Google Scholar
Ausili, A., Pennacchio, A., Staiano, M., Dattelbaum, J. D., Fessas, D., Schiraldi, A. & D'auria, S. (2013). Amino acid transport in thermophiles: characterization of an arginine-binding protein from Thermotoga maritima. 3. Conformational dynamics and stability. Journal of Photochemistry and Photobiology B 118, 66–73.Google Scholar
Ayesh, S., Shao, Y. M. & Stein, W. D. (1996). Co-operative, competitive and non-competitive interactions between modulators of P-glycoprotein. Biochimica et Biophysica Acta 1316(1), 8–18.Google Scholar
Bai, Y., Li, M. & Hwang, T. C. (2011). Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7). Journal of General Physiology 138(5), 495–507.Google Scholar
Bao, H. & Duong, F. (2012). Discovery of an auto-regulation mechanism for the maltose ABC transporter MalFGK2. PLoS ONE 7(4), e34836.Google Scholar
Basso, C., Vergani, P., Nairn, A. C. & Gadsby, D. C. (2003). Prolonged nonhydrolytic interaction of nucleotide with CFTR's NH2-terminal nucleotide binding domain and its role in channel gating. Journal of General Physiology 122(3), 333–348.Google Scholar
Beaudet, L. & Gros, P. (1995). Functional dissection of P-glycoprotein nucleotide-binding domains in chimeric and mutant proteins. Modulation of drug resistance profiles. Journal of Biological Chemistry 270(29), 17159–17170.Google Scholar
Beaudet, L., Urbatsch, I. L. & Gros, P. (1998). Mutations in the nucleotide-binding sites of P-glycoprotein that affect substrate specificity modulate substrate-induced adenosine triphosphatase activity. Biochemistry 37(25), 9073–9082.Google Scholar
Becq, F. & Chanson, M. (2013). Strategies to circumvent the CFTR defect in cystic fibrosis. Frontiers in Pharmacology 4, 108.Google Scholar
Bianchet, M. A., Ko, Y. H., Amzel, L. M. & Pedersen, P. L. (1997). Modeling of nucleotide binding domains of ABC transporter proteins based on a F1-ATPase/recA topology: structural model of the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR). Journal of Bioenergetics and Biomembrane 29(5), 503–524.Google Scholar
Biswas-Fiss, E. E., Affet, S., Ha, M. & Biswas, S. B. (2012). Retinoid binding properties of nucleotide binding domain 1 of the Stargardt disease-associated ATP binding cassette (ABC) transporter, ABCA4. Journal of Biological Chemistry 287(53), 44097–44107.Google Scholar
Borths, E. L., Locher, K. P., Lee, A. T. & Rees, D. C. (2002). The structure of Escherichia coli BtuF and binding to its cognate ATP binding cassette transporter. Proceedings of the National Academy of Sciences United States of America 99(26), 16642–16647.Google Scholar
Boyer, N. P., Higbee, D., Currin, M. B., Blakeley, L. R., Chen, C., Ablonczy, Z., Crouch, R. K. & Koutalos, Y. (2012). Lipofuscin and N-retinylidene-N-retinylethanolamine (A2E) accumulate in retinal pigment epithelium in absence of light exposure: their origin is 11-cis-retinal. Journal of Biological Chemistry 287(26), 22276–22286.Google Scholar
Bruggemann, E. P., Germann, U. A., Gottesman, M. M. & Pastan, I. (1989). Two different regions of P-glycoprotein [corrected] are photoaffinity-labeled by azidopine. Journal of Biological Chemistry 264(26), 15483–15488.Google Scholar
Chan, S., Giuroiu, I., Chernishof, I., Sawaya, M. R., Chiang, J., Gunsalus, R. P., Arbing, M. A. & Perry, L. J. (2010). Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans. Acta Crystallography Sect F 66(Pt 3), 242–250.Google Scholar
Chen, J. (2013). Molecular mechanism of the Escherichia coli maltose transporter. Current Opinion in Structural Biology 23(4), 492–498.Google Scholar
Chen, J., Lu, G., Lin, J., Davidson, A. L. & Quiocho, F. A. (2003). A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. Molecular Cell 12(3), 651–661.Google Scholar
Chong, P. A., Kota, P., Dokholyan, N. V. & Forman-Kay, J. D. (2013). Dynamics intrinsic to cystic fibrosis transmembrane conductance regulator function and stability. Cold Spring Harbor Perspectives in Medicine 3(3), a009522.Google Scholar
Csanády, L. & Töröcsik, B. (2014). Catalyst-like modulation of transition states for CFTR channel opening and closing: New stimulation strategy exploits nonequilibrium gating. Journal of General Physiology 143(2), 269–287.Google Scholar
Daus, M. L., Landmesser, H., Schlosser, A., Muller, P., Herrmann, A. & Schneider, E. (2006). ATP induces conformational changes of periplasmic loop regions of the maltose ATP-binding cassette transporter. Journal of Biological Chemistry 281(7), 3856–3865.Google Scholar
Daus, M. L., Berendt, S., Wuttge, S. & Schneider, E. (2007). Maltose binding protein (MalE) interacts with periplasmic loops P2 and P1 respectively of the MalFG subunits of the maltose ATP binding cassette transporter (MalFGK(2)) from Escherichia coli/Salmonella during the transport cycle. Molecular Microbiology 66(5), 1107–1122.Google Scholar
Davidson, A. L., Dassa, E., Orelle, C. & Chen, J. (2008). Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiology and Molecular Biology Reviews 72(2), 317–364. table of contents.Google Scholar
Dawson, R. J. & Locher, K. P. (2006). Structure of a bacterial multidrug ABC transporter. Nature 443, 180–185.Google Scholar
Devine, S. E., Ling, V. & Melera, P. W. (1992). Amino acid substitutions in the sixth transmembrane domain of P-glycoprotein alter multidrug resistance. Proceedings of the National Academy of Sciences United States of America 89(10), 4564–4568.Google Scholar
Dey, S., Ramachandra, M., Pastan, I., Gottesman, M. M. & Ambudkar, S. V. (1997). Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proceedings of the National Academy of Sciences United States of America 94(20), 10594–10599.Google Scholar
Fath, M. J. & Kolter, R. (1993). ABC transporters: bacterial exporters. Microbiological Reviews 57(4), 995–1017.Google Scholar
Felder, C. B., Graul, R. C., Lee, A. Y., Merkle, H. P. & Sadee, W. (1999). The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors. AAPS PharmSci 1(2), E2.Google Scholar
Ferry, D. R., Russell, M. A. & Cullen, M. H. (1992). P-glycoprotein possesses a 1,4-dihydropyridine-selective drug acceptor site which is alloserically coupled to a vinca-alkaloid-selective binding site. Biochemical and Biophysical Research Communications 188(1), 440–445.Google Scholar
Ferry, D. R., Malkhandi, P. J., Russell, M. A. & Kerr, D. J. (1995). Allosteric regulation of [3H]vinblastine binding to P-glycoprotein of MCF-7 ADR cells by dexniguldipine. Biochemical Pharmacology 49(12), 1851–1861.Google Scholar
Fersht, A. R. (1975). Demonstration of two active sites on a monomeric aminoacyl-tRNA synthetase. Possible roles of negative cooperativity and half-of-the-sites reactivity in oligomeric enzymes. Biochemistry 14(1), 5–12.Google Scholar
Furman, C., Mehla, J., Ananthaswamy, N., Arya, N., Kulesh, B., Kovach, I., Ambudkar, S. V. & Golin, J. (2013). The deviant ATP-binding site of the multidrug efflux pump Pdr5 plays an active role in the transport cycle. Journal of Biological Chemistry 288(42), 30420–30431.Google Scholar
Gadsby, D. C., Vergani, P. & Csanady, L. (2006). The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440(7083), 477–483.Google Scholar
Garrigos, M., Mir, L. M. & Orlowski, S. (1997). Competitive and non-competitive inhibition of the multidrug-resistance-associated P-glycoprotein ATPase – further experimental evidence for a multisite model. European Journal of Biochemistry 244(2), 664–673.Google Scholar
George, A. M. & Jones, P. M. (2011). Type II ABC permeases: are they really so different? Structure 19(11), 1540–1542.Google Scholar
George, A. M. & Jones, P. M. (2012). Perspectives on the structure-function of ABC transporters: the switch and constant contact models. Progress in Biophysics and Molecular Biology 109(3), 95–107.Google Scholar
Georges, E., Tsuruo, T. & Ling, V. (1993). Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody. Journal of Biological Chemistry 268(3), 1792–1798.Google Scholar
Gopinath, K., Venclovas, C., Ioerger, T. R., Sacchettini, J. C., Mckinney, J. D., Mizrahi, V. & Warner, D. F. (2013). A vitamin B(1)(2) transporter in Mycobacterium tuberculosis. Open Biology 3(2), 120175.Google Scholar
Gout, T. (2012). Role of ATP binding and hydrolysis in the gating of the cystic fibrosis transmembrane conductance regulator. Annals of Thoracic Medicine 7(3), 115–121.Google Scholar
Greenberger, L. M., Lisanti, C. J., Silva, J. T. & Horwitz, S. B. (1991). Domain mapping of the photoaffinity drug-binding sites in P-glycoprotein encoded by mouse mdr1b. Journal of Biological Chemistry 266(31), 20744–20751.Google Scholar
Hanrahan, J. W., Sampson, H. M. & Thomas, D. Y. (2013). Novel pharmacological strategies to treat cystic fibrosis. Trends in Pharmacological Sciences 34(2), 119–125.Google Scholar
Higgins, C. F. (1992). ABC transporters; from microorganisms to man. Annual Review of Cell Biology 8, 67–113.Google Scholar
Higgins, C. F. & Linton, K. J. (2004). The ATP switch model for ABC transporters. Nature Structural & Molecular Biology 11(10), 918–926.Google Scholar
Hoffman, L. R. & Ramsey, B. W. (2013). Cystic fibrosis therapeutics: the road ahead. Chest 143(1), 207–213.Google Scholar
Hollenstein, K., Frei, D. C. & Locher, K. P. (2007). Structure of an ABC transporter in complex with its binding protein. Nature 446(7132), 213–216.Google Scholar
Hollenstein, K., Comellas-Bigler, M., Bevers, L. E., Feiters, M. C., Meyer-Klaucke, W., Hagedoorn, P. L. & Locher, K. P. (2009). Distorted octahedral coordination of tungstate in a subfamily of specific binding proteins. Journal of Biological Inorganic Chemistry 14(5), 663–672.Google Scholar
Hoof, T., Demmer, A., Hadam, M. R., Riordan, J. R. & Tummler, B. (1994). Cystic fibrosis-type mutational analysis in the ATP-binding cassette transporter signature of human P-glycoprotein MDR1. Journal of Biological Chemistry 269(32), 20575–20583.Google Scholar
Huls, M., Russel, F. G. & Masereeuw, R. (2009). The role of ATP binding cassette transporters in tissue defense and organ regeneration. Journal of Pharmacology and Experimental Therapeutics 328(1), 3–9.Google Scholar
Hunke, S., Mourez, M., Jehanno, M., Dassa, E. & Schneider, E. (2000). ATP modulates subunit-subunit interactions in an ATP-binding cassette transporter (MalFGK2) determined by site-directed chemical cross-linking. Journal of Biological Chemistry 275(20), 15526–15534.Google Scholar
Hwang, T. C. & Kirk, K. L. (2013). The CFTR ion channel: gating, regulation, and anion permeation. Cold Spring Harbor Perspectives in Medicine 3(1), a009498.Google Scholar
Jih, K. Y. & Hwang, T. C. (2013). Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle. Proceedings of the National Academy of Sciences United States of America 110(11), 4404–4409.Google Scholar
Jin, P. Y., Lu, Y. C., Li, L. & Han, Q. F. (2012). Co action of CFTR and AQP1 increases permeability of peritoneal epithelial cells on estrogen-induced ovarian hyper stimulation syndrome. BMC Cell Biology 13, 23.Google Scholar
Jones, P. M. & George, A. M. (1998). A new structural model for P-glycoprotein. Journal of Membrane Biology 166(2), 133–147.Google Scholar
Jones, P. M. & George, A. M. (1999). Subunit interactions in ABC transporters: towards a functional architecture. FEMS Microbiology Letters 179(2), 187–202.Google Scholar
Jones, P. M. & George, A. M. (2004). The ABC transporter structure and mechanism: perspectives on recent research. Cellular and Molecular Life Sciences 61, 1–18.Google Scholar
Jones, P. M. & George, A. M. (2009). Opening of the ADP-bound active site in the ABC transporter ATPase dimer: evidence for a constant contact, alternating sites model for the catalytic cycle. Proteins 75(2), 387–396.Google Scholar
Jones, P. M. & George, A. M. (2012). Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter. Journal of Physical Chemistry A 116(11), 3004–3013.Google Scholar
Jones, P. M. & George, A. M. (2013). Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record. Critical Reviews in Biochemistry and Molecular Biology 48(1), 39–50.Google Scholar
Jones, P. M., O'mara, M. L. & George, A. M. (2009). ABC transporters: a riddle wrapped in a mystery inside an enigma. Trends in Biochemical Sciences 34(10), 520–531.Google Scholar
Kanonenberg, K., Schwarz, C. K. & Schmitt, L. (2013). Type I secretion systems – a story of appendices. Research in Microbiology 164(6), 596–604.Google Scholar
Karpowich, N., Martsinkevich, O., Millen, L., Yuan, Y. R., Dai, P. L., Macvey, K., Thomas, P. J. & Hunt, J. F. (2001). Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure (Cambridge) 9(7), 571–586.Google Scholar
Koike, K., Conseil, G., Leslie, E. M., Deeley, R. G. & Cole, S. P. (2004). Identification of proline residues in the core cytoplasmic and transmembrane regions of multidrug resistance protein 1 (MRP1/ABCC1) important for transport function, substrate specificity, and nucleotide interactions. Journal of Biological Chemistry 279(13), 12325–12336.Google Scholar
Kos, V. & Ford, R. C. (2009). The ATP-binding cassette family: a structural perspective. Cellular and Molecular Life Sciences 66(19), 3111–3126.Google Scholar
Lee, Y. H., Deka, R. K., Norgard, M. V., Radolf, J. D. & Hasemann, C. A. (1999). Treponema pallidum TroA is a periplasmic zinc-binding protein with a helical backbone. Nature Structural Biology 6(7), 628–633.Google Scholar
Letourneau, I. J., Nakajima, A., Deeley, R. G. & Cole, S. P. (2008). Role of proline 1150 in functional interactions between the membrane spanning domains and nucleotide binding domains of the MRP1 (ABCC1) transporter. Biochemical Pharmacology 75(8), 1659–1669.Google Scholar
Levitzki, A. & Koshland, D. E. Jr. (1976). The role of negative cooperativity and half-of-the-sites reactivity in enzyme regulation. Current Topics in Cellular Regulation 10, 1–40.Google Scholar
Lewinson, O., Lee, A. T., Locher, K. P. & Rees, D. C. (2010). A distinct mechanism for the ABC transporter BtuCD-BtuF revealed by the dynamics of complex formation. Nature Structural & Molecular Biology 17(3), 332–338.Google Scholar
Lewis, V. G., Ween, M. P. & Mcdevitt, C. A. (2012). The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma 249(4), 919–942.Google Scholar
Linsdell, P., Zheng, S. X. & Hanrahan, J. W. (1998). Non-pore lining amino acid side chains influence anion selectivity of the human CFTR Cl-channel expressed in mammalian cell lines. Journal of Physiology 512(Pt 1), 1–16.Google Scholar
Litman, T., Zeuthen, T., Skovsgaard, T. & Stein, W. D. (1997). Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et Biophysica Acta 1361(2), 169–176.Google Scholar
Liu, R. & Sharom, F. J. (1996). Site-directed fluorescence labeling of P-glycoprotein on cysteine residues in the nucleotide binding domains. Biochemistry 35(36), 11865–11873.Google Scholar
Locher, K. P. (2009). Structure and mechanism of ATP-binding cassette transporters. Philosophical Transaction of the Royal Society London B: Biological Sciences 364(1514), 239–245.Google Scholar
Loisel, E., Jacquamet, L., Serre, L., Bauvois, C., Ferrer, J. L., Vernet, T., Di Guilmi, A. M. & Durmort, C. (2008). AdcAII, a new pneumococcal Zn-binding protein homologous with ABC transporters: biochemical and structural analysis. Journal of Molecular Biology 381(3), 594–606.Google Scholar
Luchansky, M. S., Der, B. S., D'auria, S., Pocsfalvi, G., Iozzino, L., Marasco, D. & Dattelbaum, J. D. (2010). Amino acid transport in thermophiles: characterization of an arginine-binding protein in Thermotoga maritima. Molecular Biosystems 6(1), 142–151.Google Scholar
Maki, N., Hafkemeyer, P. & Dey, S. (2003). Allosteric modulation of human P-glycoprotein. Inhibition of transport by preventing substrate translocation and dissociation. Journal of Biological Chemistry 278(20), 18132–18139.Google Scholar
Maki, N., Moitra, K., Ghosh, P. & Dey, S. (2006a). Allosteric modulation bypasses the requirement for ATP hydrolysis in regenerating low affinity transition state conformation of human P-glycoprotein. Journal of Biological Chemistry 281(16), 10769–10777.Google Scholar
Maki, N., Moitra, K., Silver, C., Ghosh, P., Chattopadhyay, A. & Dey, S. (2006b). Modulator-induced interference in functional cross talk between the substrate and the ATP sites of human P-glycoprotein. Biochemistry 45(8), 2739–2751.Google Scholar
Manson, M. D., Boos, W., Bassford, P. J. Jr. & Rasmussen, B. A. (1985). Dependence of maltose transport and chemotaxis on the amount of maltose-binding protein. Journal of Biological Chemistry 260(17), 9727–9733.Google Scholar
Martin, C., Berridge, G., Higgins, C. F. & Callaghan, R. (1997). The multi-drug resistance reversal agent SR33557 and modulation of vinca alkaloid binding to P-glycoprotein by an allosteric interaction. British Journal of Pharmacology 122(4), 765–771.Google Scholar
Martin, C., Berridge, G., Higgins, C. F., Mistry, P., Charlton, P. & Callaghan, R. (2000a). Communication between multiple drug binding sites on P-glycoprotein. Molecular Pharmacology 58, 624–632.Google Scholar
Martin, C., Berridge, G., Mistry, P., Higgins, C. F., Charlton, P. & Callaghan, R. (2000b). Drug binding sites on P-glycoprotein are altered by ATP binding prior to nucleotide hydrolysis. Biochemistry 39, 11901–11906.Google Scholar
Merino, G., Boos, W., Shuman, H. A. & Bohl, E. (1995). The inhibition of maltose transport by the unliganded form of the maltose-binding protein of Escherichia coli: experimental findings and mathematical treatment. Journal of Theoretical Biology 177(2), 171–179.Google Scholar
Mittal, A., Boehm, S., Grutter, M. G., Bordignon, E. & Seeger, M. A. (2012). Asymmetry in the homodimeric ABC transporter MsbA recognized by a DARPin. Journal of Biological Chemistry 287, 20395–20406.Google Scholar
Mourez, M., Hofnung, M. & Dassa, E. (1997). Subunit interactions in ABC transporters: a conserved sequence in hydrophobic membrane proteins of periplasmic permeases defines an important site of interaction with the ATPase subunits. EMBO Journal 16(11), 3066–3077.Google Scholar
Oldham, M. L., Davidson, A. L. & Chen, J. (2008). Structural insights into ABC transporter mechanism. Current Opinion in Structural Biology 18(6), 726–733.Google Scholar
Orlowski, S., Mir, L. M., Belehradek, J. Jr. & Garrigos, M. (1996). Effects of steroids and verapamil on P-glycoprotein ATPase activity: progesterone, desoxycorticosterone, corticosterone and verapamil are mutually non-exclusive modulators. Biochemical Journal 317(Pt 2), 515–522.Google Scholar
Pahnke, J., Frohlich, C., Krohn, M., Schumacher, T. & Paarmann, K. (2013). Impaired mitochondrial energy production and ABC transporter function – a crucial interconnection in dementing proteopathies of the brain. Mechanisms of Ageing and Development 134(10), 506–515.Google Scholar
Parveen, Z., Stockner, T., Bentele, C., Pferschy, S., Kraupp, M., Freissmuth, M., Ecker, G. F. & Chiba, P. (2011). Molecular dissection of dual pseudosymmetric solute translocation pathways in human P-glycoprotein. Molecular Pharmacology 79(3), 443–452.Google Scholar
Pascaud, C., Garrigos, M. & Orlowski, S. (1998). Multidrug resistance transporter P-glycoprotein has distinct but interacting binding sites for cytotoxic drugs and reversing agents. Biochemical Journal 333(Pt 2), 351–358.Google Scholar
Pereira, E., Borrel, M. N., Fiallo, M. & Garnier-Suillerot, A. (1994). Non-competitive inhibition of P-glycoprotein-associated efflux of THP-adriamycin by verapamil in living K562 leukemia cells. Biochimica et Biophysica Acta 1225(2), 209–216.Google Scholar
Prossnitz, E., Gee, A. & Ames, G. F. (1989). Reconstitution of the histidine periplasmic transport system in membrane vesicles. Energy coupling and interaction between the binding protein and the membrane complex. Journal of Biological Chemistry 264(9), 5006–5014.Google Scholar
Qu, Q., Russell, P. L. & Sharom, F. J. (2003). Stoichiometry and affinity of nucleotide binding to P-glycoprotein during the catalytic cycle. Biochemistry 42(4), 1170–1177.Google Scholar
Quazi, F., Lenevich, S. & Molday, R. S. (2012). ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nature Communications 3, 925.Google Scholar
Rees, D. C., Johnson, E. & Lewinson, O. (2009). ABC transporters: the power to change. Nature Reviews Molecular Cell Biology 10(3), 218–227.Google Scholar
Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L. et al. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245(4922), 1066–1073.Google Scholar
Ritchie, T. K., Kwon, H. & Atkins, W. M. (2011). Conformational analysis of human ATP-binding cassette transporter ABCB1 in lipid nanodiscs and inhibition by the antibodies MRK16 and UIC2. Journal of Biological Chemistry 286(45), 39489–39496.Google Scholar
Rothnie, A., Callaghan, R., Deeley, R. G. & Cole, S. P. (2006). Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1). Journal of Biological Chemistry 281(20), 13906–13914.Google Scholar
Safa, A. R. (2004). Identification and characterization of the binding sites of P-glycoprotein for multidrug resistance-related drugs and modulators. Current Medicinal Chemistry: Anti-Cancer Agents 4(1), 1–17.Google Scholar
Saurin, W., Hofnung, M. & Dassa, E. (1999). Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. Journal of Molecular Evolution 48(1), 22–41.Google Scholar
Schinkel, A. H., Arceci, R. J., Smit, J. J., Wagenaar, E., Baas, F., Dolle, M., Tsuruo, T., Mechetner, E. B., Roninson, I. B. & Borst, P. (1993). Binding properties of monoclonal antibodies recognizing external epitopes of the human MDR1 P-glycoprotein. International Journal of Cancer 55(3), 478–484.Google Scholar
Schmees, G., Stein, A., Hunke, S., Landmesser, H. & Schneider, E. (1999). Functional consequences of mutations in the conserved ‘signature sequence’ of the ATP-binding-cassette protein MalK. European Journal of Biochemistry 266(2), 420–430.Google Scholar
Seelheim, P., Wullner, A. & Galla, H. J. (2013). Substrate translocation and stimulated ATP hydrolysis of human ABC transporter MRP3 show positive cooperativity and are half-coupled. Biophysical Chemistry 171, 31–37.Google Scholar
Senior, A. E. & Bhagat, S. (1998). P-glycoprotein shows strong catalytic cooperativity between the two nucleotide sites. Biochemistry 37(3), 831–836.Google Scholar
Senior, A. E., Al-Shawi, M. K. & Urbatsch, I. L. (1995). The catalytic cycle of P-glycoprotein. FEBS Letters 377, 285–289.Google Scholar
Shapiro, A. B. & Ling, V. (1997). Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. European Journal of Biochemistry 250(1), 130–137.Google Scholar
Sharma, S. & Davidson, A. L. (2000). Vanadate-induced trapping of nucleotides by purified maltose transport complex requires ATP hydrolysis. Journal of Bacteriology 182(23), 6570–6576.Google Scholar
Sharom, F. J., Yu, X., Didiodato, G. & Chu, J. W. (1996). Synthetic hydrophobic peptides are substrates for P-glycoprotein and stimulate drug transport. Biochemical Journal 320 (Pt 2), 421–428.Google Scholar
Sharom, F. J., Yu, X., Lu, P., Liu, R., Chu, J. W., Szabo, K., Muller, M., Hose, C. D., Monks, A., Varadi, A., Seprodi, J. & Sarkadi, B. (1999). Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells. Biochemical Pharmacology 58(4), 571–586.Google Scholar
Shyamala, V., Baichwal, V., Beall, E. & Ames, G. F. (1991). Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations. Journal of Biological Chemistry 266(28), 18714–18719.Google Scholar
Smith, P. C., Karpowich, N., Millen, L., Moody, J. E., Rosen, J., Thomas, P. J. & Hunt, J. F. (2002). ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Molecular Cell 10(1), 139–149.Google Scholar
Speiser, D. M. & Ames, G. F. (1991). Salmonella typhimurium histidine periplasmic permease mutations that allow transport in the absence of histidine-binding proteins. Journal of Bacteriology 173(4), 1444–1451.Google Scholar
Spoelstra, E. C., Dekker, H., Schuurhuis, G. J., Broxterman, H. J. & Lankelma, J. (1991). P-glycoprotein drug efflux pump involved in the mechanisms of intrinsic drug resistance in various colon cancer cell lines. Evidence for a saturation of active daunorubicin transport. Biochemical Pharmacology 41(3), 349–359.Google Scholar
Spoelstra, E. C., Westerhoff, H. V., Pinedo, H. M., Dekker, H. & Lankelma, J. (1994). The multidrug-resistance-reverser verapamil interferes with cellular P-glycoprotein-mediated pumping of daunorubicin as a non-competing substrate. European Journal of Biochemistry 221(1), 363–373.Google Scholar
Storm, J., O'mara, M., Crowley, E., Peall, J., Tieleman, P. D., Kerr, I. D. & Callaghan, R. (2007). Residue G346 in transmembrane segment six is involved in inter-domain communication in P-glycoprotein. Biochemistry 46(35), 9899–9910.Google Scholar
Szollosi, A., Muallem, D. R., Csanady, L. & Vergani, P. (2011). Mutant cycles at CFTR's non-canonical ATP-binding site support little interface separation during gating. Journal of General Physiology 137(6), 549–562.Google Scholar
Tamai, I. & Safa, A. R. (1991). Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells. Journal of Biological Chemistry 266(25), 16796–16800.Google Scholar
Tirado-Lee, L., Lee, A., Rees, D. C. & Pinkett, H. W. (2011). Classification of a Haemophilus influenzae ABC transporter HI1470/71 through its cognate molybdate periplasmic binding protein, MolA. Structure 19(11), 1701–1710.Google Scholar
Tsai, M. F., Shimizu, H., Sohma, Y., Li, M. & Hwang, T. C. (2009). State-dependent modulation of CFTR gating by pyrophosphate. Journal of General Physiology 133(4), 405–419.Google Scholar
Tsybovsky, Y., Molday, R. S. & Palczewski, K. (2010). The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. Advances in Experimental Medicine and Biology 703, 105–125.Google Scholar
Tsybovsky, Y., Orban, T., Molday, R. S., Taylor, D. & Palczewski, K. (2013). Molecular organization and ATP-induced conformational changes of ABCA4, the photoreceptor-specific ABC transporter. Structure 21, 1–7.Google Scholar
Vahedi-Faridi, A., Eckey, V., Scheffel, F., Alings, C., Landmesser, H., Schneider, E. & Saenger, W. (2008). Crystal structures and mutational analysis of the arginine-, lysine-, histidine-binding protein ArtJ from Geobacillus stearothermophilus. Implications for interactions of ArtJ with its cognate ATP-binding cassette transporter, Art(MP)2. Journal of Molecular Biology 375(2), 448–459.Google Scholar
van der Does, C. & Tampe, R. (2004). How do ABC transporters drive transport? Biological Chemistry 385(10), 927–933.Google Scholar
van der Heide, T. & Poolman, B. (2002). ABC transporters: one, two or four extracytoplasmic substrate-binding sites? EMBO Reports 3(10), 938–943.Google Scholar
van Veen, H. W., Margolles, A., Muller, M., Higgins, C. F. & Konings, W. N. (2000). The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating (two-cylinder engine) mechanism. EMBO Journal 19, 2503–2514.Google Scholar
Vergani, P., Lockless, S. W., Nairn, A. C. & Gadsby, D. C. (2005). CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature 433(7028), 876–880.Google Scholar
Vigonsky, E., Ovcharenko, E. & Lewinson, O. (2013). Two molybdate/tungstate ABC transporters that interact very differently with their substrate binding proteins. Proceedings of the National Academy of Sciences United States of America 110(14), 5440–5445.Google Scholar
Walker, J. E., Saraste, M., Runswick, M. J. & Gay, N. J. (1982). 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. EMBO Journal 1(8), 945–951.Google Scholar
Walter, C., Wilken, S. & Schneider, E. (1992). Characterization of site-directed mutations in conserved domains of MalK, a bacterial member of the ATP-binding cassette (ABC) family [corrected]. FEBS Letters 303(1), 41–44.Google Scholar
Wang, B., Dukarevich, M., Sun, E. I., Yen, M. R. & Saier, M. H. Jr. (2009). Membrane porters of ATP-binding cassette transport systems are polyphyletic. Journal of Membrane Biology 231(1), 1–10.Google Scholar
Wang, E. J., Casciano, C. N., Clement, R. P. & Johnson, W. W. (2000a). Cooperativity in the inhibition of P-glycoprotein-mediated daunorubicin transport: evidence for half-of-the-sites reactivity. Archives of Biochemistry and Biophysics 383(1), 91–98.Google Scholar
Wang, E. J., Casciano, C. N., Clement, R. P. & Johnson, W. W. (2000b). Two transport binding sites of P-glycoprotein are unequal yet contingent: initial rate kinetic analysis by ATP hydrolysis demonstrates intersite dependence. Biochimica et Biophysica Acta 1481(1), 63–74.Google Scholar
Wang, T., Fu, G., Pan, X., Wu, J., Gong, X., Wang, J. & Shi, Y. (2013). Structure of a bacterial energy-coupling factor transporter. Nature 497(7448), 272–276.Google Scholar
Wang, W. & Linsdell, P. (2012). Alternating access to the transmembrane domain of the ATP-binding cassette protein cystic fibrosis transmembrane conductance regulator (ABCC7). Journal of Biological Chemistry 287(13), 10156–10165.Google Scholar
Ward, A. B., Szewczyk, P., Grimard, V., Lee, C. W., Martinez, L., Doshi, R., Caya, A., Villaluz, M., Pardon, E., Cregger, C., Swartz, D. J., Falson, P. G., Urbatsch, I. L., Govaerts, C., Steyaert, J. & Chang, G. (2013). Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain. Proceedings of the National Academy of Sciences United States of America 110(33), 13386–13391.Google Scholar
Yue, H., Devidas, S. & Guggino, W. B. (2000). The two halves of CFTR form a dual-pore ion channel. Journal of Biological Chemistry 275(14), 10030–10034.Google Scholar
Zheng, W. H., Vastermark, A., Shlykov, M. A., Reddy, V., Sun, E. I. & Saier, M. H. Jr. (2013). Evolutionary relationships of ATP-Binding Cassette (ABC) uptake porters. BMC Microbiology 13, 98.Google Scholar
Zhou, Y., Gottesman, M. M. & Pastan, I. (1999). The extracellular loop between TM5 and TM6 of P-glycoprotein is required for reactivity with monoclonal antibody UIC2. Archives of Biochemistry and Biophysics 367(1), 74–80.Google Scholar