ATP-binding Cassette Exporters: Structure and Mechanism with a Focus on P-glycoprotein and MRP1

Author(s): Maite Rocío Arana , Guillermo Alejandro Altenberg* .

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 7 , 2019

  Journal Home
Translate in Chinese

Abstract:

Background: Proteins that belong to the ATP-binding cassette superfamily include transporters that mediate the efflux of substrates from cells. Among these exporters, P-glycoprotein and MRP1 are involved in cancer multidrug resistance, protection from endo and xenobiotics, determination of drug pharmacokinetics, and the pathophysiology of a variety of disorders.

Objective: To review the information available on ATP-binding cassette exporters, with a focus on Pglycoprotein, MRP1 and related proteins. We describe tissue localization and function of these transporters in health and disease, and discuss the mechanisms of substrate transport. We also correlate recent structural information with the function of the exporters, and discuss details of their molecular mechanism with a focus on the nucleotide-binding domains.

Methods: Evaluation of selected publications on the structure and function of ATP-binding cassette proteins.

Conclusions: Conformational changes on the nucleotide-binding domains side of the exporters switch the accessibility of the substrate-binding pocket between the inside and outside, which is coupled to substrate efflux. However, there is no agreement on the magnitude and nature of the changes at the nucleotide- binding domains side that drive the alternate-accessibility. Comparison of the structures of Pglycoprotein and MRP1 helps explain differences in substrate selectivity and the bases for polyspecificity. P-glycoprotein substrates are hydrophobic and/or weak bases, and polyspecificity is explained by a flexible hydrophobic multi-binding site that has a few acidic patches. MRP1 substrates are mostly organic acids, and its polyspecificity is due to a single bipartite binding site that is flexible and displays positive charge.

Keywords: ATP-binding cassette, multidrug resistance, nucleotide-binding domain, dimer, hydrolysis, Pglycoprotein, MRP1, ABCB, ABCC.

[1]
Khamisipour, G.; Jadidi-Niaragh, F.; Jahromi, A.S.; Zandi, K.; Hojjat-Farsangi, M. Mechanisms of tumor cell resistance to the current targeted-therapy agents. Tumour Biol., 2016, 37(8), 10021-10039.
[2]
Rice, A.J.; Park, A.; Pinkett, H.W. Diversity in ABC transporters: type I, II and III importers. Crit. Rev. Biochem. Mol. Biol., 2014, 49(5), 426-437.
[3]
Slot, A.J.; Molinski, S.V.; Cole, S.P. Mammalian multidrug-resistance proteins (MRPs). Essays Biochem., 2011, 50(1), 179-207.
[4]
Cole, S.P. Multidrug resistance protein 1 (MRP1, ABCC1), a “multitasking” ATP-binding cassette (ABC) transporter. J. Biol. Chem., 2014, 289(45), 30880-30888.
[5]
Taylor, N.M.I.; Manolaridis, I.; Jackson, S.M.; Kowal, J.; Stahlberg, H.; Locher, K.P. Structure of the human multidrug transporter ABCG2. Nature, 2017, 546(7659), 504-509.
[6]
Kunjachan, S.; Rychlik, B.; Storm, G.; Kiessling, F.; Lammers, T. Multidrug resistance: Physiological principles and nanomedical solutions. Adv. Drug Deliv. Rev., 2013, 65(13-14), 1852-1865.
[7]
Choi, Y.H.; Yu, A.M. ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr. Pharm. Des., 2014, 20(5), 793-807.
[8]
Deeley, R.G.; Westlake, C.; Cole, S.P. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol. Rev., 2006, 86(3), 849-899.
[9]
ter Beek, J.; Guskov, A.; Slotboom, D.J. Structural diversity of ABC transporters. J. Gen. Physiol., 2014, 143(4), 419-435.
[10]
Walker, J.E.; Saraste, M.; Runswick, M.J.; Gay, N.J. 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 J., 1982, 1(8), 945-951.
[11]
Juliano, R.L.; Ling, V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta, 1976, 455(1), 152-162.
[12]
Schinkel, A.H.; Borst, P. Multidrug resistance mediated by P-glycoproteins. Semin. Cancer Biol., 1991, 2(4), 213-226.
[13]
Ushigome, F.; Takanaga, H.; Matsuo, H.; Yanai, S.; Tsukimori, K.; Nakano, H.; Uchiumi, T.; Nakamura, T.; Kuwano, M.; Ohtani, H.; Sawada, Y. Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein. Eur. J. Pharmacol., 2000, 408(1), 1-10.
[14]
Gatmaitan, Z.C.; Arias, I.M. Structure and function of P-glycoprotein in normal liver and small intestine. Adv. Pharmacol., 1993, 24, 77-97.
[15]
Begley, D.J.; Lechardeur, D.; Chen, Z.D.; Rollinson, C.; Bardoul, M.; Roux, F.; Scherman, D.; Abbott, N.J. Functional expression of P-glycoprotein in an immortalised cell line of rat brain endothelial cells, RBE4. J. Neurochem., 1996, 67(3), 988-995.
[16]
Lee, C.H. Induction of P-glycoprotein mRNA transcripts by cycloheximide in animal tissues: evidence that class I Pgp is transcriptionally regulated whereas class II Pgp is post-transcriptionally regulated. Mol. Cell. Biochem., 2001, 216(1-2), 103-110.
[17]
Tsuji, A.; Terasaki, T.; Takabatake, Y.; Tenda, Y.; Tamai, I.; Yamashima, T.; Moritani, S.; Tsuruo, T.; Yamashita, J. P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci., 1992, 51(18), 1427-1437.
[18]
Rao, V.V.; Dahlheimer, J.L.; Bardgett, M.E.; Snyder, A.Z.; Finch, R.A.; Sartorelli, A.C.; Piwnica-Worms, D. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc. Natl. Acad. Sci. USA, 1999, 96(7), 3900-3905.
[19]
Schinkel, A.H.; Wagenaar, E.; Mol, C.A.; van Deemter, L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J. Clin. Invest., 1996, 97(11), 2517-2524.
[20]
Smit, J.J.; Schinkel, A.H.; Mol, C.A.; Majoor, D.; Mooi, W.J.; Jongsma, A.P.; Lincke, C.R.; Borst, P. Tissue distribution of the human MDR3 P-glycoprotein. Lab. Invest., 1994, 71(5), 638-649.
[21]
Chan, L.M.; Lowes, S.; Hirst, B.H. The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur. J. Pharm. Sci., 2004, 21(1), 25-51.
[22]
Mahringer, A.; Fricker, G. ABC transporters at the blood-brain barrier. Expert Opin. Drug Metab. Toxicol., 2016, 12(5), 499-508.
[23]
Joshi, A.A.; Vaidya, S.S.; St-Pierre, M.V.; Mikheev, A.M.; Desino, K.E.; Nyandege, A.N.; Audus, K.L.; Unadkat, J.D.; Gerk, P.M. Placental ABC transporters: Biological impact and pharmaceutical significance. Pharm. Res., 2016, 33(12), 2847-2878.
[24]
Raub, T.J. P-glycoprotein recognition of substrates and circumvention through rational drug design. Mol. Pharm., 2006, 3(1), 3-25.
[25]
Wang, R.B.; Kuo, C.L.; Lien, L.L.; Lien, E.J. Structure-activity relationship: analyses of p-glycoprotein substrates and inhibitors. J. Clin. Pharm. Ther., 2003, 28(3), 203-228.
[26]
Sharom, F.J.; Lugo, M.R.; Eckford, P.D. New insights into the drug binding, transport and lipid flippase activities of the p-glycoprotein multidrug transporter. J. Bioenerg. Biomembr., 2005, 37(6), 481-487.
[27]
Ledwitch, K.V.; Roberts, A.G. Cardiovascular ion channel inhibitor drug-drug interactions with P-glycoprotein. AAPS J., 2017, 19(2), 409-420.
[28]
Foy, M.; Sperati, C.J.; Lucas, G.M.; Estrella, M.M. Drug interactions and antiretroviral drug monitoring. Curr. HIV/AIDS Rep., 2014, 11(3), 212-222.
[29]
Yang, X.; Liu, K. P-gp Inhibition-based strategies for modulating pharmacokinetics of anticancer drugs: An update. Curr. Drug Metab., 2016, 17(8), 806-826.
[30]
Nakanishi, T.; Tamai, I. Interaction of drug or food with drug transporters in intestine and liver. Curr. Drug Metab., 2015, 16(9), 753-764.
[31]
Chandra, P.; Brouwer, K.L. The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm. Res., 2004, 21(5), 719-735.
[32]
Tamaki, A.; Ierano, C.; Szakacs, G.; Robey, R.W.; Bates, S.E. The controversial role of ABC transporters in clinical oncology. Essays Biochem., 2011, 50(1), 209-232.
[33]
Leslie, E.M.; Deeley, R.G.; Cole, S.P. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol. Appl. Pharmacol., 2005, 204(3), 216-237.
[34]
Cole, S.P.; Bhardwaj, G.; Gerlach, J.H.; Mackie, J.E.; Grant, C.E.; Almquist, K.C.; Stewart, A.J.; Kurz, E.U.; Duncan, A.M.; Deeley, R.G. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science, 1992, 258(5088), 1650-1654.
[35]
Valente, R.C.; Capella, L.S.; Nascimento, C.R.; Lopes, A.G.; Capella, M.A. Modulation of multidrug resistance protein (MRP1/ABCC1) expression: a novel physiological role for ouabain. Cell Biol. Toxicol., 2007, 23(6), 421-427.
[36]
Berggren, S.; Gall, C.; Wollnitz, N.; Ekelund, M.; Karlbom, U.; Hoogstraate, J.; Schrenk, D.; Lennernas, H. Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine. Mol. Pharm., 2007, 4(2), 252-257.
[37]
Nies, A.T.; Jedlitschky, G.; Konig, J.; Herold-Mende, C.; Steiner, H.H.; Schmitt, H.P.; Keppler, D. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience, 2004, 129(2), 349-360.
[38]
Albermann, N.; Schmitz-Winnenthal, F.H. Z’Graggen, K.; Volk, C.; Hoffmann, M.M.; Haefeli, W.E.; Weiss, J. Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver. Biochem. Pharmacol., 2005, 70(6), 949-958.
[39]
Buchler, M.; Konig, J.; Brom, M.; Kartenbeck, J.; Spring, H.; Horie, T.; Keppler, D. cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J. Biol. Chem., 1996, 271(25), 15091-15098.
[40]
Schaub, T.P.; Kartenbeck, J.; Konig, J.; Vogel, O.; Witzgall, R.; Kriz, W.; Keppler, D. Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J. Am. Soc. Nephrol., 1997, 8(8), 1213-1221.
[41]
Mottino, A.D.; Hoffman, T.; Jennes, L.; Vore, M. Expression and localization of multidrug resistant protein mrp2 in rat small intestine. J. Pharmacol. Exp. Ther., 2000, 293(3), 717-723.
[42]
Potschka, H.; Fedrowitz, M.; Loscher, W. Multidrug resistance protein MRP2 contributes to blood-brain barrier function and restricts antiepileptic drug activity. J. Pharmacol. Exp. Ther., 2003, 306(1), 124-131.
[43]
Korita, P.V.; Wakai, T.; Shirai, Y.; Matsuda, Y.; Sakata, J.; Takamura, M.; Yano, M.; Sanpei, A.; Aoyagi, Y.; Hatakeyama, K.; Ajioka, Y. Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma. Oncol. Rep., 2010, 23(4), 965-972.
[44]
Yamasaki, M.; Makino, T.; Masuzawa, T.; Kurokawa, Y.; Miyata, H.; Takiguchi, S.; Nakajima, K.; Fujiwara, Y.; Matsuura, N.; Mori, M.; Doki, Y. Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma. Br. J. Cancer, 2011, 104(4), 707-713.
[45]
Toh, S.; Wada, M.; Uchiumi, T.; Inokuchi, A.; Makino, Y.; Horie, Y.; Adachi, Y.; Sakisaka, S.; Kuwano, M. Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am. J. Hum. Genet., 1999, 64(3), 739-746.
[46]
Konig, J.; Rost, D.; Cui, Y.; Keppler, D. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology, 1999, 29(4), 1156-1163.
[47]
Borst, P.; Zelcer, N.; van de Wetering, K. MRP2 and 3 in health and disease. Cancer Lett., 2006, 234(1), 51-61.
[48]
Rost, D.; Konig, J.; Weiss, G.; Klar, E.; Stremmel, W.; Keppler, D. Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia. Gastroenterol., 2001, 121(5), 1203-1208.
[49]
Zollner, G.; Wagner, M.; Fickert, P.; Silbert, D.; Fuchsbichler, A.; Zatloukal, K.; Denk, H.; Trauner, M. Hepatobiliary transporter expression in human hepatocellular carcinoma. Liver Int., 2005, 25(2), 367-379.
[50]
Benderra, Z.; Faussat, A.M.; Sayada, L.; Perrot, J.Y.; Tang, R.; Chaoui, D.; Morjani, H.; Marzac, C.; Marie, J.P.; Legrand, O. MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin. Cancer Res., 2005, 11(21), 7764-7772.
[51]
Takahashi, K.; Tatsunami, R.; Sato, K.; Tampo, Y. Multidrug resistance associated protein 1 together with glutathione plays a protective role against 4-hydroxy-2-nonenal-induced oxidative stress in bovine aortic endothelial cells. Biol. Pharm. Bull., 2012, 35(8), 1269-1274.
[52]
Ji, B.; Ito, K.; Suzuki, H.; Sugiyama, Y.; Horie, T. Multidrug resistance-associated protein2 (MRP2) plays an important role in the biliary excretion of glutathione conjugates of 4-hydroxynonenal. Free Radic. Biol. Med., 2002, 33(3), 370-378.
[53]
Mottino, A.D.; Hoffman, T.; Jennes, L.; Cao, J.; Vore, M. Expression of multidrug resistance-associated protein 2 in small intestine from pregnant and postpartum rats. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 280(6), G1261-G1273.
[54]
Choudhuri, S.; Cherrington, N.J.; Li, N.; Klaassen, C.D. Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats. Drug Metab. Dispos., 2003, 31(11), 1337-1345.
[55]
Bauer, B.; Hartz, A.M.; Lucking, J.R.; Yang, X.; Pollack, G.M.; Miller, D.S. Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTpi, at the blood-brain barrier. J. Cereb. Blood Flow Metab., 2008, 28(6), 1222-1234.
[56]
Chen, Z.; Shi, T.; Zhang, L.; Zhu, P.; Deng, M.; Huang, C.; Hu, T.; Jiang, L.; Li, J. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett., 2016, 370(1), 153-164.
[57]
Doyle, L.A.; Yang, W.; Abruzzo, L.V.; Krogmann, T.; Gao, Y.; Rishi, A.K.; Ross, D.D. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. USA, 1998, 95(26), 15665-15670.
[58]
Mao, Q.; Unadkat, J.D. Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport--an update. AAPS J., 2015, 17(1), 65-82.
[59]
Ishikawa, T.; Aw, W.; Kaneko, K. Metabolic interactions of purine derivatives with human ABC transporter ABCG2: Genetic testing to assess gout risk. Pharmaceuticals (Basel), 2013, 6(11), 1347-1360.
[60]
Bruhn, O.; Cascorbi, I. Polymorphisms of the drug transporters ABCB1, ABCG2, ABCC2 and ABCC3 and their impact on drug bioavailability and clinical relevance. Expert Opin. Drug Metab. Toxicol., 2014, 10(10), 1337-1354.
[61]
van Herwaarden, A.E.; Wagenaar, E.; Merino, G.; Jonker, J.W.; Rosing, H.; Beijnen, J.H.; Schinkel, A.H. Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. Mol. Cell. Biol., 2007, 27(4), 1247-1253.
[62]
Jonker, J.W.; Merino, G.; Musters, S.; van Herwaarden, A.E.; Bolscher, E.; Wagenaar, E.; Mesman, E.; Dale, T.C.; Schinkel, A.H. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat. Med., 2005, 11(2), 127-129.
[63]
Keppler, D. Cholestasis and the role of basolateral efflux pumps. Z. Gastroenterol., 2011, 49(12), 1553-1557.
[64]
Ghanem, C.I.; Ruiz, M.L.; Villanueva, S.S.; Luquita, M.G.; Catania, V.A.; Jones, B.; Bengochea, L.A.; Vore, M.; Mottino, A.D. Shift from biliary to urinary elimination of acetaminophen-glucuronide in acetaminophen-pretreated rats. J. Pharmacol. Exp. Ther., 2005, 315(3), 987-995.
[65]
Gottesman, M.M.; Ambudkar, S.V. Overview: ABC transporters and human disease. J. Bioenerg. Biomembr., 2001, 33(6), 453-458.
[66]
Sharom, F.J. The P-glycoprotein multidrug transporter. Essays Biochem., 2011, 50(1), 161-178.
[67]
Roepe, P.D. What is the precise role of human MDR 1 protein in chemotherapeutic drug resistance? Curr. Pharm. Des., 2000, 6(3), 241-260.
[68]
Young, G.; Reuss, L.; Altenberg, G.A. Altered intracellular pH regulation in cells with high levels of P-glycoprotein expression. Int. J. Biochem. Mol. Biol., 2011, 2(3), 219-227.
[69]
Altenberg, G.A.; Young, G.; Horton, J.K.; Glass, D.; Belli, J.A.; Reuss, L. Changes in intra- or extracellular pH do not mediate P-glycoprotein-dependent multidrug resistance. Proc. Natl. Acad. Sci. USA, 1993, 90(20), 9735-9738.
[70]
Hoffman, M.M.; Wei, L.Y.; Roepe, P.D. Are altered pHi and membrane potential in hu MDR 1 transfectants sufficient to cause MDR protein-mediated multidrug resistance? J. Gen. Physiol., 1996, 108(4), 295-313.
[71]
Howard, E.M.; Roepe, P.D. Purified human MDR 1 modulates membrane potential in reconstituted proteoliposomes. Biochemistry, 2003, 42(12), 3544-3555.
[72]
Singh, H.; Velamakanni, S.; Deery, M.J.; Howard, J.; Wei, S.L.; van Veen, H.W. ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled. Nat. Commun., 2016, 7, 12387.
[73]
Vanoye, C.G.; Castro, A.F.; Pourcher, T.; Reuss, L.; Altenberg, G.A. Phosphorylation of P-glycoprotein by PKA and PKC modulates swelling-activated Cl- currents. Am. J. Physiol., 1999, 276(2 Pt 1), C370-C378.
[74]
Yang, Y.; Wu, N.; Wang, Z.; Zhang, F.; Tian, R.; Ji, W.; Ren, X.; Niu, R. Rack1 mediates the interaction of Pglycoprotein with Anxa2 and regulates migration and invasion of multidrug-resistant breast cancer cells. Int. J. Mol. Sci, 2016, 17(10), pi: E1718.
[75]
Bryan, J.; Munoz, A.; Zhang, X.; Dufer, M.; Drews, G.; Krippeit-Drews, P.; Aguilar-Bryan, L. ABCC8 and ABCC9: ABC transporters that regulate K+ channels. Pflugers Arch., 2007, 453(5), 703-718.
[76]
Li, N.; Wu, J.X.; Ding, D.; Cheng, J.; Gao, N.; Chen, L. Structure of a Pancreatic ATP-Sensitive Potassium Channel. Cell,, 2017, 168(1-2), 101-110 e110.
[77]
Martin, G.M.; Yoshioka, C.; Rex, E.A.; Fay, J.F.; Xie, Q.; Whorton, M.R.; Chen, J.Z.; Shyng, S.L. Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating. eLife, 2017, 6, e24149.
[78]
Raviv, Y.; Pollard, H.B.; Bruggemann, E.P.; Pastan, I.; Gottesman, M.M. Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. J. Biol. Chem., 1990, 265(7), 3975-3980.
[79]
Johnson, Z.L.; Chen, J. Structural basis of substrate recognition by the multidrug resistance protein MRP1. Cell, 2017, 168(6), 1075-1085. e9.
[80]
Ramu, A.; Pollard, H.B.; Rosario, L.M. Doxorubicin resistance in P388 leukemia--evidence for reduced drug influx. Int. J. Cancer, 1989, 44(3), 539-547.
[81]
Shalinsky, D.R.; Jekunen, A.P.; Alcaraz, J.E.; Christen, R.D.; Kim, S.; Khatibi, S.; Howell, S.B. Regulation of initial vinblastine influx by P-glycoprotein. Br. J. Cancer, 1993, 67(1), 30-36.
[82]
Altenberg, G.A.; Vanoye, C.G.; Horton, J.K.; Reuss, L. Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells: evidence against direct drug extrusion from the plasma membrane. Proc. Natl. Acad. Sci. USA, 1994, 91(11), 4654-4657.
[83]
Smith, P.C.; Karpowich, N.; Millen, L.; Moody, J.E.; Rosen, J.; Thomas, P.J.; Hunt, J.F. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol. Cell, 2002, 10(1), 139-149.
[84]
Huang, W.; Liao, J.L. Catalytic Mechanism of the Maltose Transporter Hydrolyzing ATP. Biochemistry, 2016, 55(1), 224-231.
[85]
Hwang, T.C.; Sheppard, D.N. Gating of the CFTR Cl- channel by ATP-driven nucleotide-binding domain dimerisation. J. Physiol., 2009, 587(Pt 10), 2151-2161.
[86]
Sauna, Z.E.; Kim, I.W.; Nandigama, K.; Kopp, S.; Chiba, P.; Ambudkar, S.V. Catalytic cycle of ATP hydrolysis by P-glycoprotein: evidence for formation of the E.S reaction intermediate with ATP-gamma-S, a nonhydrolyzable analogue of ATP. Biochemistry, 2007, 46(48), 13787-13799.
[87]
Esser, L.; Zhou, F.; Pluchino, K.M.; Shiloach, J.; Ma, J.; Tang, W.K.; Gutierrez, C.; Zhang, A.; Shukla, S.; Madigan, J.P.; Zhou, T.; Kwong, P.D.; Ambudkar, S.V.; Gottesman, M.M.; Xia, D. Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity. J. Biol. Chem., 2017, 292(2), 446-461.
[88]
Gyimesi, G.; Ramachandran, S.; Kota, P.; Dokholyan, N.V.; Sarkadi, B.; Hegedus, T. ATP hydrolysis at one of the two sites in ABC transporters initiates transport related conformational transitions. Biochim. Biophys. Acta, 2011, 1808(12), 2954-2964.
[89]
Wen, P.C.; Tajkhorshid, E. Dimer opening of the nucleotide binding domains of ABC transporters after ATP hydrolysis. Biophys. J., 2008, 95(11), 5100-5110.
[90]
Dawson, R.J.; Locher, K.P. Structure of a bacterial multidrug ABC transporter. Nature, 2006, 443(7108), 180-185.
[91]
Jones, P.M.; George, A.M. 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, 2009, 75(2), 387-396.
[92]
Jones, P.M.; O’Mara, M.L.; George, A.M. ABC transporters: a riddle wrapped in a mystery inside an enigma. Trends Biochem. Sci., 2009, 34(10), 520-531.
[93]
Moody, J.E.; Millen, L.; Binns, D.; Hunt, J.F.; Thomas, P.J. Cooperative, ATP-dependent association of the nucleotide binding cassettes during the catalytic cycle of ATP-binding cassette transporters. J. Biol. Chem., 2002, 277(24), 21111-21114.
[94]
Janas, E.; Hofacker, M.; Chen, M.; Gompf, S.; van der Does, C.; Tampe, R. The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p. J. Biol. Chem., 2003, 278(29), 26862-26869.
[95]
Vergani, P.; Lockless, S.W.; Nairn, A.C.; Gadsby, D.C. CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature, 2005, 433(7028), 876-880.
[96]
Zoghbi, M.E.; Altenberg, G.A. Hydrolysis at one of the two nucleotide-binding sites drives the dissociation of ATP-binding cassette nucleotide-binding domain dimers. J. Biol. Chem., 2013, 288(47), 34259-34265.
[97]
Zoghbi, M.E.; Krishnan, S.; Altenberg, G.A. Dissociation of ATP-binding cassette nucleotide-binding domain dimers into monomers during the hydrolysis cycle. J. Biol. Chem., 2012, 287(18), 14994-15000.
[98]
Zoghbi, M.E.; Altenberg, G.A. ATP binding to two sites is necessary for dimerization of nucleotide-binding domains of ABC proteins. Biochem. Biophys. Res. Commun., 2014, 443(1), 97-102.
[99]
Urbatsch, I.L.; al-Shawi, M.K.; Senior, A.E. Characterization of the ATPase activity of purified Chinese hamster P-glycoprotein. Biochemistry, 1994, 33(23), 7069-7076.
[100]
Biswas, E.E. Nucleotide binding domain 1 of the human retinal ABC transporter functions as a general ribonucleotidase. Biochemistry, 2001, 40(28), 8181-8187.
[101]
de Wet, H.; Mikhailov, M.V.; Fotinou, C.; Dreger, M.; Craig, T.J.; Venien-Bryan, C.; Ashcroft, F.M. Studies of the ATPase activity of the ABC protein SUR1. FEBS J., 2007, 274(14), 3532-3544.
[102]
Fendley, G.A.; Urbatsch, I.L.; Sutton, R.B.; Zoghbi, M.E.; Altenberg, G.A. Nucleotide dependence of the dimerization of ATP binding cassette nucleotide binding domains. Biochem. Biophys. Res. Commun., 2016, 480(2), 268-272.
[103]
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. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science, 2009, 323(5922), 1718-1722.
[104]
Li, J.; Jaimes, K.F.; Aller, S.G. Refined structures of mouse P-glycoprotein. Protein Sci., 2014, 23(1), 34-46.
[105]
Jin, M.S.; Oldham, M.L.; Zhang, Q.; Chen, J. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature, 2012, 490(7421), 566-569.
[106]
Szewczyk, P.; Tao, H.; McGrath, A.P.; Villaluz, M.; Rees, S.D.; Lee, S.C.; Doshi, R.; Urbatsch, I.L.; Zhang, Q.; Chang, G. Snapshots of ligand entry, malleable binding and induced helical movement in P-glycoprotein. Acta Crystallogr. D., 2015, 71(Pt 3), 732-741.
[107]
Gutmann, D.A.; Ward, A.; Urbatsch, I.L.; Chang, G.; van Veen, H.W. Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1. Trends Biochem. Sci., 2010, 35(1), 36-42.
[108]
Shapiro, A.B.; Fox, K.; Lam, P.; Ling, V. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. Eur. J. Biochem., 1999, 259(3), 841-850.
[109]
Martin, C.; Berridge, G.; Higgins, C.F.; Mistry, P.; Charlton, P.; Callaghan, R. Communication between multiple drug binding sites on P-glycoprotein. Mol. Pharmacol., 2000, 58(3), 624-632.
[110]
Safa, A.R. Identification and characterization of the binding sites of P-glycoprotein for multidrug resistance-related drugs and modulators. Curr. Med. Chem. Anticancer Agents, 2004, 4(1), 1-17.
[111]
Martinez, L.; Arnaud, O.; Henin, E.; Tao, H.; Chaptal, V.; Doshi, R.; Andrieu, T.; Dussurgey, S.; Tod, M.; Di Pietro, A.; Zhang, Q.; Chang, G.; Falson, P. Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein. The FEBS J., 2014, 281(3), 673-682.
[112]
Shapiro, A.B.; Ling, V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur. J. Biochem., 1997, 250(1), 130-137.
[113]
Hulpke, S.; Tomioka, M.; Kremmer, E.; Ueda, K.; Abele, R.; Tampe, R. Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex. Cell. Mol. Life Sci., 2012, 69(19), 3317-3327.
[114]
Liu, F.; Zhang, Z.; Csanady, L.; Gadsby, D.C.; Chen, J. Molecular Structure of the Human CFTR Ion Channel Cell, 2012, 169(1), 85-95 e88.
[115]
Bakos, E.; Evers, R.; Szakacs, G.; Tusnady, G.E.; Welker, E.; Szabo, K.; de Haas, M.; van Deemter, L.; Borst, P.; Varadi, A.; Sarkadi, B. Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain. J. Biol. Chem., 1998, 273(48), 32167-32175.
[116]
Bakos, E.; Evers, R.; Calenda, G.; Tusnady, G.E.; Szakacs, G.; Varadi, A.; Sarkadi, B. Characterization of the amino-terminal regions in the human multidrug resistance protein (MRP1). J. Cell Sci., 2000, 113(Pt 24), 4451-4461.
[117]
Oldham, M.L.; Chen, J. Crystal structure of the maltose transporter in a pretranslocation intermediate state. Science, 2011, 332(6034), 1202-1205.
[118]
Zhang, Z.; Liu, F.; Chen, J. Conformational Changes of CFTR upon Phosphorylation and ATP Binding. Cell, 2017, 170(3), 483-491 e488.
[119]
Qian, H.; Zhao, X.; Cao, P.; Lei, J.; Yan, N.; Gong, X. Structure of the Human Lipid Exporter ABCA1. Cell, 2017, 169(7), 1228-1239 e1210.
[120]
Lee, J.Y.; Kinch, L.N.; Borek, D.M.; Wang, J.; Wang, J.; Urbatsch, I.L.; Xie, X.S.; Grishin, N.V.; Cohen, J.C.; Otwinowski, Z.; Hobbs, H.H.; Rosenbaum, D.M. Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature, 2016, 533(7604), 561-564.
[121]
Telbisz, A.; Hegedus, C.; Varadi, A.; Sarkadi, B.; Ozvegy-Laczka, C. Regulation of the function of the human ABCG2 multidrug transporter by cholesterol and bile acids: effects of mutations in potential substrate and steroid binding sites. Drug Metab. Dispos., 2014, 42(4), 575-585.
[122]
Ward, A.; Reyes, C.L.; Yu, J.; Roth, C.B.; Chang, G. Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc. Natl. Acad. Sci. USA, 2007, 104(48), 19005-19010.
[123]
Brooks-Wilson, A.; Marcil, M.; Clee, S.M.; Zhang, L.H.; Roomp, K.; van Dam, M.; Yu, L.; Brewer, C.; Collins, J.A.; Molhuizen, H.O.; Loubser, O.; Ouelette, B.F.; Fichter, K.; Ashbourne-Excoffon, K.J.; Sensen, C.W.; Scherer, S.; Mott, S.; Denis, M.; Martindale, D.; Frohlich, J.; Morgan, K.; Koop, B.; Pimstone, S.; Kastelein, J.J.; Genest, J., Jr; Hayden, M.R. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat. Genet., 1999, 22(4), 336-345.
[124]
Perez, C.; Gerber, S.; Boilevin, J.; Bucher, M.; Darbre, T.; Aebi, M.; Reymond, J.L.; Locher, K.P. Structure and mechanism of an active lipid-linked oligosaccharide flippase. Nature, 2015, 524(7566), 433-438.
[125]
Hopfner, K.P.; Karcher, A.; Shin, D.S.; Craig, L.; Arthur, L.M.; Carney, J.P.; Tainer, J.A. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell, 2000, 101(7), 789-800.
[126]
Zoghbi, M.E.; Fuson, K.L.; Sutton, R.B.; Altenberg, G.A. Kinetics of the association/dissociation cycle of an ATP-binding cassette nucleotide-binding domain. J. Biol. Chem., 2012, 287(6), 4157-4164.
[127]
Zoghbi, M.E.; Cooper, R.S.; Altenberg, G.A. The Lipid Bilayer Modulates the Structure and Function of an ATP-binding Cassette Exporter. J. Biol. Chem., 2016, 291(9), 4453-4461.
[128]
Moeller, A.; Lee, S.C.; Tao, H.; Speir, J.A.; Chang, G.; Urbatsch, I.L.; Potter, C.S.; Carragher, B.; Zhang, Q. Distinct Conformational Spectrum of Homologous Multidrug ABC Transporters. Structure, 2015, 23(3), 450-460.
[129]
Marcoux, J.; Wang, S.C.; Politis, A.; Reading, E.; Ma, J.; Biggin, P.C.; Zhou, M.; Tao, H.; Zhang, Q.; Chang, G.; Morgner, N.; Robinson, C.V. Mass spectrometry reveals synergistic effects of nucleotides, lipids, and drugs binding to a multidrug resistance efflux pump. Proc. Natl. Acad. Sci. USA, 2013, 110(24), 9704-9709.
[130]
Pan, L.; Aller, S.G. Equilibrated atomic models of outward-facing P-glycoprotein and effect of ATP binding on structural dynamics. Sci. Rep., 2015, 5, 7880.
[131]
Lee, J.Y.; Urbatsch, I.L.; Senior, A.E.; Wilkens, S. Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy. J. Biol. Chem., 2008, 283(9), 5769-5779.
[132]
Lee, J.Y.; Urbatsch, I.L.; Senior, A.E.; Wilkens, S. Projection structure of P-glycoprotein by electron microscopy. Evidence for a closed conformation of the nucleotide binding domains. J. Biol. Chem., 2002, 277(42), 40125-40131.
[133]
Cooper, R.S.; Altenberg, G.A. Association/ dissociation of the nucleotide-binding domains of the ATP-binding cassette protein MsbA measured during continuous hydrolysis. J. Biol. Chem., 2013, 288(29), 20785-20796.
[134]
Zou, P.; Bortolus, M.; McHaourab, H.S. Conformational cycle of the ABC transporter MsbA in liposomes: detailed analysis using double electron-electron resonance spectroscopy. J. Mol. Biol., 2009, 393(3), 586-597.
[135]
Verhalen, B.; Dastvan, R.; Thangapandian, S.; Peskova, Y.; Koteiche, H.A.; Nakamoto, R.K.; Tajkhorshid, E.; McHaourab, H.S. Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein. Nature, 2017, 543(7647), 738-741.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 7
Year: 2019
Page: [1062 - 1078]
Pages: 17
DOI: 10.2174/0929867324666171012105143
Price: $58

Article Metrics

PDF: 41
HTML: 3