Plant lessons: Exploring ABCB functionality through structural modeling

Frontiers in Plant Science

Volumn 2, Issue JAN, 2012, Pages

  Bailly, Aurélien ^a,b   Yang, Haibing ^c   Martinoia, Enrico ^b   Geisler, Markus ^a,b   Murphy, Angus S ^c  

^a UNIVERSITY OF FRIBOURG   (Switzerland)

^b Botanical Institute of the University of Basel   (Switzerland)

^c PURDUE UNIVERSITY   (United States)

Author keywords

ABCB exporter; ABCB importer; Auxin; Structural modeling; Substrate docking

Indexed keywords

EID: 84863840544     PISSN: None     EISSN: 1664462X     Source Type: Journal    
DOI: 10.3389/fpls.2011.00108     Document Type: Article

References (100)

1. Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L., and Chang, G. (2009). Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323, 1718-1722.
2. Ashkenazy, H., Erez, E., Martz, E., Pupko, T., and Ben-Tal, N. (2010). ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 38, W529-W533.
3. Bachas, S., Eginton, C., Gunio, D., and Wade, H. (2011). Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR. Proc. Natl. Acad. Sci. U.S.A. 108, 11046-11051.
4. Bailly, A., Sovero, V., Vincenzetti, V., Santelia, D., Bartnik, D., Koenig, B. W., Mancuso, S., Martinoia, E., and Geisler, M. (2008). Modulation of P-glycoproteins by auxin transport inhibitors is mediated by interaction with immunophilins. J. Biol. Chem. 283, 21817-21826.
5. Baker, N. A., Sept, D., Joseph, S., Holst, M. J., and Mccammon, J. A. (2001). Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. U.S.A. 98, 10037-10041.
6. Becker, J. P., Van Bambeke, F., Tulkens, P. M., and Prevost, M. (2010). Dynamics and structural changes induced by ATP binding in SAV1866, a bacterial ABC exporter. J. Phys. Chem. B 114, 15948-15957.
7. Benkert, P., Tosatto, S. C., and Schomburg, D. (2008). QMEAN: a comprehensive scoring function for model quality assessment. Proteins 71, 261-277.
8. Bessadok, A., Garcia, E., Jacquet, H., Martin, S., Garrigues, A., Loiseau, N., Andre, F., Orlowski, S., and Vivaudou, M. (2011). Recognition of sulfonylurea receptor (ABCC8/9) ligands by the multidrug resistance transporter P-glycoprotein (ABCB1): functional similarities based on common structural features between two multispecific ABC proteins. J. Biol. Chem. 286, 3552-3569.
9. Blakeslee, J. J., Bandyopadhyay, A., Lee, O. R., Mravec, J., Titapiwatanakun, B., Sauer, M., Makam, S. N., Cheng, Y., Bouchard, R., Adamec, J., Geisler, M., Nagashima, A., Sakai, T., Martinoia, E., Friml, J., Peer, W. A., and Murphy, A. S. (2007). Interactions among PIN-FORMED and P-glycoprotein auxin transporters in Arabidopsis. Plant Cell 19, 131-147.
10. Borowski, E., Bontemps-Gracz, M. M., and Piwkowska, A. (2005). Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells. Acta Biochim. Pol. 52, 609-627.
11. Bouchard, R., Bailly, A., Blakeslee, J. J., Oehring, S. C., Vincenzetti, V., Lee, O. R., Paponov, I., Palme, K., Mancuso, S., Murphy, A. S., Schulz, B., and Geisler, M. (2006). Immunophilin-like TWISTED DWARF1 modulates auxin efflux activities of Arabidopsis P-glycoproteins. J. Biol. Chem. 281, 30603-30612.
12. Cho, M., Lee, S. H., and Cho, H. T. (2007). P-glycoprotein4 displays auxin efflux transporter-like action in Arabidopsis root hair cells and tobacco cells. Plant Cell 19, 3930-3943.
13. Colovos, C., and Yeates, T. O. (1993). Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci. 2, 1511-1519.
14. Corpet, F. (1988). Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 16, 10881-10890.
15. Dawson, R. J., Hollenstein, K., and Locher, K. P. (2007). Uptake or extrusion: crystal structures of full ABC transporters suggest a common mechanism. Mol. Microbiol. 65, 250-257.
16. Dawson, R. J., and Locher, K. P. (2006). Structure of a bacterial multidrug ABC transporter. Nature 443, 180-185.
17. Dawson, R. J., and Locher, K. P. (2007). Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett. 581, 935-938.
18. De Smet, I., Voss, U., Lau, S., Wilson, M., Shao, N., Timme, R. E., Swarup, R., Kerr, I., Hodgman, C., Bock, R., Bennett, M., Jurgens, G., and Beeckman, T. (2011). Unraveling the evolution of auxin signaling. Plant Physiol. 155, 209-221.
19. Dey, S., Hafkemeyer, P., Pastan, I., and Gottesman, M. M. (1999). A single amino acid residue contributes to distinct mechanisms of inhibition of the human multidrug transporter by stereoisomers of the dopamine receptor antagonist flupentixol. Biochemistry 38, 6630-6639.
20. Eswar, N., Webb, B., Marti-Renom, M. A., Madhusudhan, M. S., Eramian, D., Shen, M. Y., Pieper, U., and Sali, A. (2006). Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinformatics Chap. 5, Unit 5.6.1-5.6.30.
21. Ferro, N., Bredow, T., Jacobsen, H. J., and Reinard, T. (2010). Route to novel auxin: auxin chemical space toward biological correlation carriers. Chem. Rev. 110, 4690-4708.
22. Ferro, N., Gallegos, A., Bultinck, P., Jacobsen, H. J., Carbo-Dorca, R., and Reinard, T. (2006). Coulomb and overlap self-similarities: a comparative selectivity analysis of structure-function relationships for auxin-like molecules. J. Chem. Inf. Model. 46, 1751-1762.
23. Garrigos, M., Mir, L. M., and Orlowski, S. (1997). Competitive and non-competitive inhibition of the multidrug-resistance-associated P-glycoprotein ATPase-further experimental evidence for a multisite model. Eur. J. Biochem. 244, 664-673.
24. Geisler, M., Blakeslee, J. J., Bouchard, R., Lee, O. R., Vincenzetti, V., Bandyopadhyay, A., Titapiwatanakun, B., Peer, W. A., Bailly, A., Richards, E. L., Ejendal, K. F., Smith, A. P., Baroux, C., Grossniklaus, U., Muller, A., Hrycyna, C. A., Dudler, R., Murphy, A. S., and Martinoia, E. (2005). Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1. Plant J. 44, 179-194.
25. Geisler, M., Kolukisaoglu, H. U., Bouchard, R., Billion, K., Berger, J., Saal, B., Frangne, N., Koncz-Kalman, Z., Koncz, C., Dudler, R., Blakeslee, J. J., Murphy, A. S., Martinoia, E., and Schulz, B. (2003). TWISTED DWARF1, a unique plasma membrane-anchored immunophilin-like protein, interacts with Arabidopsis multidrug resistance-like transporters AtPGP1 and AtPGP19. Mol. Biol. Cell 14, 4238-4249.
26. Geisler, M., and Murphy, A. S. (2006). The ABC of auxin transport: the role of p-glycoproteins in plant development. FEBS Lett. 580, 1094-1102.
27. Gruol, D. J., Bernd, J., Phippard, A. E., Ojima, I., and Bernacki, R. J. (2001). The use of a novel taxane-based P-glycoprotein inhibitor to identify mutations that alter the interaction of the protein with paclitaxel. Mol. Pharmacol. 60, 104-113.
28. Gutmann, D. A., Ward, A., Urbatsch, I. L., Chang, G., and Van Veen, H. W. (2010). Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1. Trends Biochem. Sci. 35, 36-42.
29. Higgins, C. F. (2001). ABC transporters: physiology, structure and mechanism-an overview. Res. Microbiol. 152, 205-210.
30. Hollenstein, K., Dawson, R. J., and Locher, K. P. (2007). Structure and mechanism of ABC transporter proteins. Curr. Opin. Struct. Biol. 17, 412-418.
31. Hooft, R. W., Vriend, G., Sander, C., and Abola, E. E. (1996). Errors in protein structures. Nature 381, 272.
32. Hopfner, K. P., Karcher, A., Shin, D. S., Craig, L., Arthur, L. M., Carney, J. P., and Tainer, J. A. (2000). Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101, 789-800.
33. Hrycyna, C. A., and Gottesman, M. M. (1998). Multidrug ABC transporters from bacteria to man: an emerging hypothesis for the universality of molecular mechanism and function. Drug Resist. Updat. 1, 81-83.
34. Jasinski, M., Ducos, E., Martinoia, E., and Boutry, M. (2003). The ATP-binding cassette transporters: structure, function, and gene family comparison between rice and Arabidopsis. Plant Physiol. 131, 1169-1177.
35. Keitt, G. W., and Baker, R. A. (1966). Auxin activity of substituted benzoic acids and their effect on polar auxin transport. Plant Physiol. 41, 1561.
36. Kelch, D. G., Driskell, A., and Mishler, B. (2004). "Inferring phylogeny using genomic characters: a case study using land plant plastomes, " Molecular Systematics of Bryophytes, eds V. H. B. Goffinet and R. Magill (St. Louis, MO: Missouri Botanical Garden Press), 3-12.
37. Kim, J. Y., Henrichs, S., Bailly, A., Vincenzetti, V., Sovero, V., Mancuso, S., Pollmann, S., Kim, D., Geisler, M., and Nam, H. G. (2010). Identification of an ABCB/P-glycoprotein-specific inhibitor of auxin transport by chemical genomics. J. Biol. Chem. 285, 23309-23317.
38. Kimura, Y., Kodan, A., Matsuo, M., and Ueda, K. (2007). Cholesterol fill-in model: mechanism for substrate recognition by ABC proteins. J. Bioenerg. Biomembr. 39, 447-452.
39. Klepsch, F., Chiba, P., and Ecker, G. F. (2011). Exhaustive sampling of docking poses reveals binding hypotheses for propafenone type inhibitors of P-glycoprotein. PLoS Comput. Biol. 7, e1002036. doi:10.1371/journal.pcbi.1002036
40. Knoller, A. S., Blakeslee, J. J., Richards, E. L., Peer, W. A., and Murphy, A. S. (2010). Brachytic2/ZmABCB1 functions in IAA export from intercalary meristems. J. Exp. Bot. 61, 3689-3696.
41. Kubes, M., Yang, H., Richter, G. L., Cheng, Y., Mlodzinska, E., Wang, X., Blakeslee, J., Carraro, N., Petrasek, J., Zazimalova, E., Hoyerova, K., Peer, W. A., and Murphy, A. S. (2011). The Arabidopsis concentration-dependent influx/efflux transporter ABCB4 regulates cellular auxin levels in the root epidermis. Plant J. doi: 10.1111/j.1365-313X.2011.04818.x
42. Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., Mcgettigan, P. A., Mcwilliam, H., Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J., and Higgins, D. G. (2007). Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947-2948.
43. Laskowski, R. A., Macarthur, M. W., Moss, D. S., and Thornton, J. M. (1993). Procheck-a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283-291.
44. Lee, M., Choi, Y., Burla, B., Kim, Y. Y., Jeon, B., Maeshima, M., Yoo, J. Y., Martinoia, E., and Lee, Y. (2008). The ABC transporter AtABCB14 is a malate importer and modulates stomatal response to CO2. Nat. Cell Biol. 10, 1217-1223.
45. Li, Y., Yuan, H., Yang, K., Xu, W., Tang, W., and Li, X. (2010). The structure and functions of P-glycoprotein. Curr. Med. Chem. 17, 786-800.
46. Linton, K. J., and Higgins, C. F. (2007). Structure and function of ABC transporters: the ATP switch provides flexible control. Pflugers Arch. 453, 555-567.
47. Lobler, M., and Klambt, D. (1985). Auxin-binding protein from coleoptile membranes of corn (Zea mays-L).10.1. Purification by immunological methods and characterization. J. Biol. Chem. 260, 9848-9853.
48. Locher, K. P. (2004). Structure and mechanism of ABC transporters. Curr. Opin. Struct. Biol. 14, 426-431.
49. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2003a). Drug binding in human P-glycoprotein causes conformational changes in both nucleotide-binding domains. J. Biol. Chem. 278, 1575-1578.
50. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2003b). Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding. J. Biol. Chem. 278, 13603-13606.
51. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2004). Processing mutations located throughout the human multidrug resistance P-glycoprotein disrupt interactions between the nucleotide binding domains. J. Biol. Chem. 279, 38395-38401.
52. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2005). ATP hydrolysis promotes interactions between the extracellular ends of transmembrane segments 1 and 11 of human multidrug resistance P-glycoprotein. Biochemistry 44, 10250-10258.
53. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2006a). Transmembrane segment 1 of human P-glycoprotein contributes to the drug-binding pocket. Biochem. J. 396, 537-545.
54. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2006b). Transmembrane segment 7 of human P-glycoprotein forms part of the drug-binding pocket. Biochem. J. 399, 351-359.
55. Loo, T. W., and Clarke, D. M. (1995). Rapid purification of human P-glycoprotein mutants expressed transiently in HEK 293 cells by nickel-chelate chromatography and characterization of their drug-stimulated ATPase activities. J. Biol. Chem. 270, 21449-21452.
56. Loo, T. W., and Clarke, D. M. (1997). Drug-stimulated ATPase activity of human P-glycoprotein requires movement between transmembrane segments 6 and 12. J. Biol. Chem. 272, 20986-20989.
57. Loo, T. W., and Clarke, D. M. (2000). Identification of residues within the drug-binding domain of the human multidrug resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane. J. Biol. Chem. 275, 39272-39278.
58. Loo, T. W., and Clarke, D. M. (2001). Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil. J. Biol. Chem. 276, 14972-14979.
59. Martin, C., Higgins, C. F., and Callaghan, R. (2001). The vinblastine binding site adopts high-and low-affinity conformations during a transport cycle of P-glycoprotein. Biochemistry 40, 15733-15742.
60. Martinoia, E., Klein, M., Geisler, M., Bovet, L., Forestier, C., Kolukisaoglu, U., Muller-Rober, B., and Schulz, B. (2002). Multifunctionality of plant ABC transporters-more than just detoxifiers. Planta 214, 345-355.
61. Mravec, J., Kubes, M., Bielach, A., Gaykova, V., Petrasek, J., Skupa, P., Chand, S., Benkova, E., Zazimalova, E., and Friml, J. (2008). Interaction of PIN and PGP transport mechanisms in auxin distribution-dependent development. Development 135, 3345-3354.
62. Muday, G. K., Brunn, S. A., Haworth, P., and Subramanian, M. (1993). Evidence for a single naphthylphthalamic acid binding site on the zucchini plasma membrane. Plant Physiol. 103, 449-456.
63. Multani, D. S., Briggs, S. P., Chamberlin, M. A., Blakeslee, J. J., Murphy, A. S., and Johal, G. S. (2003). Loss of an MDR transporter in compact stalks of maize br2 and sorghum dw3 mutants. Science 302, 81-84.
64. Nagashima, A., Uehara, Y., and Sakai, T. (2008). The ABC subfamily B auxin transporter AtABCB19 is involved in the inhibitory effects of N-1-naphthyphthalamic acid on the phototropic and gravitropic responses of Arabidopsis hypocotyls. Plant Cell Physiol. 49, 1250-1255.
65. Newberry, K. J., Huffman, J. L., Miller, M. C., Vazquez-Laslop, N., Neyfakh, A. A., and Brennan, R. G. (2008). Structures of BmrR-drug complexes reveal a rigid multidrug binding pocket and transcription activation through tyrosine expulsion. J. Biol. Chem. 283, 26795-26804.
66. Noh, B., Murphy, A. S., and Spalding, E. P. (2001). Multidrug resistance-like genes of Arabidopsis required for auxin transport and auxin-mediated development. Plant Cell 13, 2441-2454.
67. O'Connor, R., Clynes, M., Dowling, P., O'donovan, N., and O'driscoll, L. (2007). Drug resistance in cancer-searching for mechanisms, markers and therapeutic agents. Expert Opin. Drug Metab. Toxicol. 3, 805-817.
68. Oldham, M. L., and Chen, J. (2011a). Crystal structure of the maltose transporter in a pretranslocation intermediate state. Science 332, 1202-1205.
69. Oldham, M. L., and Chen, J. (2011b). Snapshots of the maltose transporter during ATP hydrolysis. Proc. Natl. Acad. Sci. U.S.A. 108, 15152-15156.
70. Oldham, M. L., Khare, D., Quiocho, F. A., Davidson, A. L., and Chen, J. (2007). Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450, 515-521.
71. Pajeva, I. K., Globisch, C., and Wiese, M. (2009). Comparison of the inward-and outward-open homology models and ligand binding of human P-glycoprotein. FEBS J. 276, 7016-7026.
72. Petrasek, J., and Friml, J. (2009). Auxin transport routes in plant development. Development 136, 2675-2688.
73. Petrek, M., Kosinova, P., Koca, J., and Otyepka, M. (2007). MOLE: a Voronoi diagram-based explorer of molecular channels, pores, and tunnels. Structure 15, 1357-1363.
74. Pleban, K., Kopp, S., Csaszar, E., Peer, M., Hrebicek, T., Rizzi, A., Ecker, G. F., and Chiba, P. (2005). P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach. Mol. Pharmacol. 67, 365-374.
75. Raven, J. A. (1975). Transport of indoleacetic-acid in plant-cells in relation to Ph and electrical potential gradients, and its significance for polar IAA transport. New Phytol. 74, 163-172.
76. Rea, P. A. (2007). Plant ATP-binding cassette transporters. Annu. Rev. Plant Biol. 58, 347-375.
77. Rojas-Pierce, M., Titapiwatanakun, B., Sohn, E. J., Fang, F., Larive, C. K., Blakeslee, J., Cheng, Y., Cutler, S. R., Peer, W. A., Murphy, A. S., and Raikhel, N. V. (2007). Arabidopsis P-glycoprotein19 participates in the inhibition of gravitropism by gravacin. Chem. Biol. 14, 1366-1376.
78. Rosenberg, M. F., Callaghan, R., Modok, S., Higgins, C. F., and Ford, R. C. (2005). Three-dimensional structure of P-glycoprotein: the transmembrane regions adopt an asymmetric configuration in the nucleotide-bound state. J. Biol. Chem. 280, 2857-2862.
79. Rothnie, A., Storm, J., Campbell, J., Linton, K. J., Kerr, I. D., and Callaghan, R. (2004). The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein. J. Biol. Chem. 279, 34913-34921.
80. Rubery, P. H., and Sheldrake, A. R. (1974). Carrier-mediated auxin transport. Planta 118, 101-121.
81. Sakurai, A., Onishi, Y., Hirano, H., Seigneuret, M., Obanayama, K., Kim, G., Liew, E. L., Sakaeda, T., Yoshiura, K., Niikawa, N., Sakurai, M., and Ishikawa, T. (2007). Quantitative structure-activity relationship analysis and molecular dynamics simulation to functionally validate nonsynonymous polymorphisms of human ABC transporter ABCB1 (P-glycoprotein/MDR1). Biochemistry 46, 7678-7693.
82. Sali, A., and Blundell, T. L. (1993). Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815.
83. Sanchez-Fernandez, R., Davies, T. G., Coleman, J. O., and Rea, P. A. (2001a). The Arabidopsis thaliana ABC protein superfamily, a complete inventory. J. Biol. Chem. 276, 30231-30244.
84. Sanchez-Fernandez, R., Rea, P. A., Davies, T. G., and Coleman, J. O. (2001b). Do plants have more genes than humans? Yes, when it comes to ABC proteins. Trends Plant Sci. 6, 347-348.
85. Santelia, D., Vincenzetti, V., Azzarello, E., Bovet, L., Fukao, Y., Duchtig, P., Mancuso, S., Martinoia, E., and Geisler, M. (2005). MDR-like ABC transporter AtPGP4 is involved in auxin-mediated lateral root and root hair development. FEBS Lett. 579, 5399-5406.
86. Seeliger, D., and de Groot, B. L. (2010). Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J. Comput. Aided Mol. Des. 24, 417-422.
87. Shapiro, A. B., and Ling, V. (1997). Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur. J. Biochem. 250, 130-137.
88. Sharom, F. J. (2008). ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics 9, 105-127.
89. Storm, J., Modok, S., O'mara, M. L., Tieleman, D. P., Kerr, I. D., and Callaghan, R. (2008). Cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labeling. Biochemistry 47, 3615-3624.
90. Sugiyama, A., Shitan, N., Sato, S., Nakamura, Y., Tabata, S., and Yazaki, K. (2006). Genome-wide analysis of ATP-binding cassette (ABC) proteins in a model legume plant, Lotus japonicus: comparison with Arabidopsis ABC protein family. DNA Res. 13, 205-228.
91. Sussman, M. R., and Gardner, G. (1980). Solubilization of the receptor for N-1-naphthylphthalamic acid. Plant Physiol. 66, 1074-1078.
92. Tan, X., Calderon-Villalobos, L. I., Sharon, M., Zheng, C., Robinson, C. V., Estelle, M., and Zheng, N. (2007). Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature 446, 640-645.
93. Terasaka, K., Blakeslee, J. J., Titapiwatanakun, B., Peer, W. A., Bandyopadhyay, A., Makam, S. N., Lee, O. R., Richards, E. L., Murphy, A. S., Sato, F., and Yazaki, K. (2005). PGP4, an ATP binding cassette P-glycoprotein, catalyzes auxin transport in Arabidopsis thaliana roots. Plant Cell 17, 2922-2939.
94. Theodoulou, F. L. (2000). Plant ABC transporters. Biochim. Biophys. Acta 1465, 79-103.
95. Titapiwatanakun, B., and Murphy, A. S. (2009). Post-transcriptional regulation of auxin transport proteins: cellular trafficking, protein phosphorylation, protein maturation, ubiquitination, and membrane composition. J. Exp. Bot. 60, 1093-1107.
96. Wang, H. Y., and Lin, R. C. (2005). Two homologous ATP-binding cassette transporter proteins, AtMDR1 and AtPGP1, regulate Arabidopsis photomorphogenesis and root development by mediating polar auxin transport. Plant Physiol. 138, 949-964.
97. Ward, A., Reyes, C. L., Yu, J., Roth, C. B., and Chang, G. (2007). Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc. Natl. Acad. Sci. U.S.A. 104, 19005-19010.
98. Wu, G., Lewis, D. R., and Spalding, E. P. (2007). Mutations in Arabidopsis multidrug resistance-like ABC transporters separate the roles of acropetal and basipetal auxin transport in lateral root development. Plant Cell 19, 1826-1837.
99. Yang, H., and Murphy, A. S. (2009). Functional expression and characterization of Arabidopsis ABCB, AUX 1 and PIN auxin transporters in Schizosaccharomyces pombe. Plant J. 59, 179-191.
100. Zazimalova, E., Murphy, A. S., Yang, H., Hoyerova, K., and Hosek, P. (2010). Auxin transporters-why so many? Cold Spring Harb. Perspect. Biol. 2, a001552.