Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion


Autoři: Katalin Goda aff001;  Yaprak Dönmez-Cakil aff002;  Szabolcs Tarapcsák aff001;  Gábor Szalóki aff001;  Dániel Szöllősi aff002;  Zahida Parveen aff005;  Dóra Türk aff007;  Gergely Szakács aff007;  Peter Chiba aff005;  Thomas Stockner aff002
Působiště autorů: Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem tér, Debrecen, Hungary aff001;  Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Waehringerstrasse, Vienna, Austria aff002;  Department of Histology and Embryology, Faculty of Medicine, Maltepe University, Maltepe, Istanbul, Turkey aff003;  Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Egyetem tér, Debrecen, Hungary aff004;  Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Waehringerstrasse, Vienna, Austria aff005;  Department of Biochemistry, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa, Pakistan aff006;  Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok körútja, Budapest, Hungary aff007;  Institute of Cancer Research, Medical University of Vienna, Borschkegasse, Vienna, Austria aff008
Vyšlo v časopise: Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009016
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009016

Souhrn

Several ABC exporters carry a degenerate nucleotide binding site (NBS) that is unable to hydrolyze ATP at a rate sufficient for sustaining transport activity. A hallmark of a degenerate NBS is the lack of the catalytic glutamate in the Walker B motif in the nucleotide binding domain (NBD). The multidrug resistance transporter ABCB1 (P-glycoprotein) has two canonical NBSs, and mutation of the catalytic glutamate E556 in NBS1 renders ABCB1 transport-incompetent. In contrast, the closely related bile salt export pump ABCB11 (BSEP), which shares 49% sequence identity with ABCB1, naturally contains a methionine in place of the catalytic glutamate. The NBD-NBD interfaces of ABCB1 and ABCB11 differ only in four residues, all within NBS1. Mutation of the catalytic glutamate in ABCB1 results in the occlusion of ATP in NBS1, leading to the arrest of the transport cycle. Here we show that despite the catalytic glutamate mutation (E556M), ABCB1 regains its ATP-dependent transport activity, when three additional diverging residues are also replaced. Molecular dynamics simulations revealed that the rescue of ATPase activity is due to the modified geometry of NBS1, resulting in a weaker interaction with ATP, which allows the quadruple mutant to evade the conformationally locked pre-hydrolytic state to proceed to ATP-driven transport. In summary, we show that ABCB1 can be transformed into an active transporter with only one functional catalytic site by preventing the formation of the ATP-locked pre-hydrolytic state in the non-canonical site.

Klíčová slova:

Adenosine triphosphatase – ATP hydrolysis – Cell membranes – Glutamate – Hydrolysis – NIH 3T3 cells – Sequence motif analysis – Nucleotides


Zdroje

1. Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992;8: 67–113. doi: 10.1146/annurev.cb.08.110192.000435 1282354

2. Rees DC, Johnson E, Lewinson O. ABC transporters: the power to change. Nat Rev Mol Cell Biol. 2009;10: 218–227. doi: 10.1038/nrm2646 19234479

3. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11: 1156–1166. doi: 10.1101/gr.184901 11435397

4. Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins. Biochim Biophys Acta-Biomembr. 1999;1461: 237–262. doi: 10.1016/S0005-2736(99)00161-3

5. Seeger MA, van Veen HW. Molecular basis of multidrug transport by ABC transporters. Biochim Biophys Acta BBA—Proteins Proteomics. 2009;1794: 725–737. doi: 10.1016/j.bbapap.2008.12.004 19135557

6. Holland IB, A. Blight M. ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. J Mol Biol. 1999;293: 381–399. doi: 10.1006/jmbi.1999.2993 10529352

7. Dawson RJP, Locher KP. Structure of a bacterial multidrug ABC transporter. Nature. 2006;443: 180–185. doi: 10.1038/nature05155 16943773

8. Oldham ML, Khare D, Quiocho F a, Davidson AL, Chen J. Crystal structure of a catalytic intermediate of the maltose transporter. Nature. 2007;450: 515–21. doi: 10.1038/nature06264 18033289

9. Lee J-Y, Kinch LN, Borek DM, Wang J, Wang J, Urbatsch IL, et al. Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature. 2016;533: 561–564. doi: 10.1038/nature17666 27144356

10. Locher KP, Lee AT, Rees DC. The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism. Science. 2002;296: 1091–1098. doi: 10.1126/science.1071142 12004122

11. Kim Y, Chen J. Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation. Science. 2018;359: 915–919. doi: 10.1126/science.aar7389 29371429

12. Esser L, Zhou F, Pluchino KM, Shiloach J, Ma J, Tang W-K, et al. Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity. J Biol Chem. 2017;292: 446–461. doi: 10.1074/jbc.M116.755884 27864369

13. Alam A, Kowal J, Broude E, Roninson I, Locher KP. Structural insight into substrate and inhibitor discrimination by human P-glycoprotein. Science. 2019;363: 753–756. doi: 10.1126/science.aav7102 30765569

14. Alam A, Küng R, Kowal J, McLeod RA, Tremp N, Broude EV, et al. Structure of a zosuquidar and UIC2-bound human-mouse chimeric ABCB1. Proc Natl Acad Sci U S A. 2018;115: E1973–E1982. doi: 10.1073/pnas.1717044115 29440498

15. Oldham ML, Grigorieff N, Chen J. Structure of the transporter associated with antigen processing trapped by herpes simplex virus. eLife. 2016;5. doi: 10.7554/eLife.21829 27935481

16. Shintre CA, Pike ACW, Li Q, Kim J-I, Barr AJ, Goubin S, et al. Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proc Natl Acad Sci U S A. 2013;110: 9710–5. doi: 10.1073/pnas.1217042110 23716676

17. Wang L, Hou W-T, Chen L, Jiang Y-L, Xu D, Sun L, et al. Cryo-EM structure of human bile salts exporter ABCB11. Cell Res. 2020. doi: 10.1038/s41422-020-0302-0 32203132

18. Smith PC, Karpowich N, Millen L, Moody JE, Rosen J, Thomas PJ, et al. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol Cell. 2002;10: 139–149. doi: 10.1016/s1097-2765(02)00576-2 12150914

19. Urbatsch IL, Tyndall GA, Tombline G, Senior AE. P-glycoprotein catalytic mechanism: studies of the ADP-vanadate inhibited state. J Biol Chem. 2003;278: 23171–23179. doi: 10.1074/jbc.M301957200 12670938

20. Janas E, Hofacker M, Chen M, Gompf S, van der Does C, Tampé R. The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p. J Biol Chem. 2003;278: 26862–26869. doi: 10.1074/jbc.M301227200 12746444

21. Szöllősi D, Rose-Sperling D, Hellmich UA, Stockner T. Comparison of mechanistic transport cycle models of ABC exporters. Biochim Biophys Acta BBA—Biomembr. 2018;1860: 818–832. doi: 10.1016/j.bbamem.2017.10.028 29097275

22. Verhalen B, Dastvan R, Thangapandian S, Peskova Y, Koteiche HA, Nakamoto RK, et al. Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein. Nature. 2017;543: 738–741. doi: 10.1038/nature21414 28289287

23. Zoghbi ME, Mok L, Swartz DJ, Singh A, Fendley GA, Urbatsch IL, et al. Substrate-induced conformational changes in the nucleotide-binding domains of lipid bilayer-associated P-glycoprotein during ATP hydrolysis. J Biol Chem. 2017;292: 20412–20424. doi: 10.1074/jbc.M117.814186 29018094

24. Moeller A, Lee SC, Tao H, Speir JA, Chang G, Urbatsch IL, et al. Distinct conformational spectrum of homologous multidrug ABC transporters. Struct Lond Engl 1993. 2015;23: 450–460. doi: 10.1016/j.str.2014.12.013 25661651

25. Loo TW, Bartlett MC, Clarke DM. Human P-glycoprotein Contains a Greasy Ball-and-Socket Joint at the Second Transmission Interface. J Biol Chem. 2013;288: 20326–20333. doi: 10.1074/jbc.M113.484550 23733192

26. Loo TW, Clarke DM. Attachment of a “molecular spring” restores drug-stimulated ATPase activity to P-glycoprotein lacking both Q loop glutamines. Biochem Biophys Res Commun. 2017;483: 366–370. doi: 10.1016/j.bbrc.2016.12.137 28025146

27. Kerr ID. Structure and association of ATP-binding cassette transporter nucleotide-binding domains. Biochim Biophys Acta. 2002;1561: 47–64. doi: 10.1016/s0304-4157(01)00008-9 11988180

28. Jin MS, Oldham ML, Zhang Q, Chen J. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature. 2012;490: 566–569. doi: 10.1038/nature11448 23000902

29. Ernst R, Koch J, Horn C, Tampé R, Schmitt L. Engineering ATPase activity in the isolated ABC cassette of human TAP1. J Biol Chem. 2006;281: 27471–27480. doi: 10.1074/jbc.M601131200 16864587

30. Zaitseva J, Jenewein S, Jumpertz T, Holland IB, Schmitt L. H662 is the linchpin of ATP hydrolysis in the nucleotide-binding domain of the ABC transporter HlyB. EMBO J. 2005;24: 1901–1910. doi: 10.1038/sj.emboj.7600657 15889153

31. Tombline G, Bartholomew LA, Urbatsch IL, Senior AE. Combined mutation of catalytic glutamate residues in the two nucleotide binding domains of P-glycoprotein generates a conformation that binds ATP and ADP tightly. J Biol Chem. 2004;279: 31212–31220. doi: 10.1074/jbc.M404689200 15159388

32. Procko E, Ferrin-O’Connell I, Ng S-L, Gaudet R. Distinct structural and functional properties of the ATPase sites in an asymmetric ABC transporter. Mol Cell. 2006;24: 51–62. doi: 10.1016/j.molcel.2006.07.034 17018292

33. Sauna ZE, Müller M, Peng X-H, Ambudkar SV. Importance of the conserved Walker B glutamate residues, 556 and 1201, for the completion of the catalytic cycle of ATP hydrolysis by human P-glycoprotein (ABCB1). Biochemistry. 2002;41: 13989–4000. doi: 10.1021/bi026626e 12437356

34. Tombline G, Bartholomew L a, Tyndall G a, Gimi K, Urbatsch IL, Senior AE. Properties of P-glycoprotein with mutations in the “catalytic carboxylate” glutamate residues. J Biol Chem. 2004;279: 46518–26. doi: 10.1074/jbc.M408052200 15326176

35. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455: 152–62. doi: 10.1016/0005-2736(76)90160-7 990323

36. Gerloff T, Stieger B, Hagenbuch B, Madon J, Landmann L, Roth J, et al. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem. 1998;273: 10046–50. doi: 10.1074/jbc.273.16.10046 9545351

37. Senior AE, al-Shawi MK, Urbatsch IL. The catalytic cycle of P-glycoprotein. FEBS Lett. 1995;377: 285–289. doi: 10.1016/0014-5793(95)01345-8 8549739

38. O’Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D, McVeigh R, et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 2016;44: D733–45. doi: 10.1093/nar/gkv1189 26553804

39. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, et al. Clustal W and Clustal X version 2.0. Bioinformatics. 2007;23: 2947–2948. doi: 10.1093/bioinformatics/btm404 17846036

40. Benner SA, Cohen MA, Gonnet GH. Amino acid substitution during functionally constrained divergent evolution of protein sequences. Protein Eng. 1994;7: 1323–32. doi: 10.1093/protein/7.11.1323 7700864

41. Shi T, Wrin J, Reeder J, Liu D, Ring DB. High-Affinity Monoclonal Antibodies against P-Glycoprotein. Clin Immunol Immunopathol. 1995;76: 44–51. doi: 10.1006/clin.1995.1086 7541735

42. Ward A, Reyes CL, Yu J, Roth CB, Chang G. Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc Natl Acad Sci U S A. 2007;104: 19005–19010. doi: 10.1073/pnas.0709388104 18024585

43. Mechetner EB, Schott B, Morse BS, Stein WD, Druley T, Davis KA, et al. P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity. Proc Natl Acad Sci U S A. 1997;94: 12908–12913. doi: 10.1073/pnas.94.24.12908 9371774

44. Nagy H, Goda K, Arceci R, Cianfriglia M, Mechetner E, Szabo G. P-Glycoprotein conformational changes detected by antibody competition. Eur J Biochem. 2001;268: 2416–2420. doi: 10.1046/j.1432-1327.2001.02122.x 11298761

45. Sauna ZE, Kim I-W, Nandigama K, Kopp S, Chiba P, Ambudkar SV. 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: 13787–99. doi: 10.1021/bi701385t 17988154

46. Loo TW, Bartlett MC, Clarke DM. Drug binding in human P-glycoprotein causes conformational changes in both nucleotide-binding domains. J Biol Chem. 2003;278: 1575–8. doi: 10.1074/jbc.M211307200 12421806

47. al-Shawi MK, Senior AE. Characterization of the adenosine triphosphatase activity of Chinese hamster P-glycoprotein. J Biol Chem. 1993;268: 4197–4206. 8095047

48. Ramachandra M, Ambudkar SV, Chen D, Hrycyna CA, Dey S, Gottesman MM, et al. Human P-glycoprotein exhibits reduced affinity for substrates during a catalytic transition state. Biochemistry. 1998;37: 5010–5019. doi: 10.1021/bi973045u 9538020

49. Wonderen JH van, McMahon RM, O’Mara ML, McDevitt CA, Thomson AJ, Kerr ID, et al. The central cavity of ABCB1 undergoes alternating access during ATP hydrolysis. FEBS J. 2014;281: 2190–2201. doi: 10.1111/febs.12773 24597976

50. Loo TW, Clarke DM. Cross-linking of human multidrug resistance P-glycoprotein by the substrate, tris-(2-maleimidoethyl)amine, is altered by ATP hydrolysis. Evidence for rotation of a transmembrane helix. J Biol Chem. 2001;276: 31800–5. doi: 10.1074/jbc.M103498200 11429407

51. Barsony O, Szaloki G, Turk D, Tarapcsak S, Gutay-Toth Z, Bacso Z, et al. A single active catalytic site is sufficient to promote transport in P-glycoprotein. Sci Rep. 2016;6: 24810. doi: 10.1038/srep24810 27117502

52. Druley TE, Stein WD, Ruth A, Roninson IB. P-glycoprotein-mediated colchicine resistance in different cell lines correlates with the effects of colchicine on P-glycoprotein conformation. Biochemistry. 2001;40: 4323–4331. doi: 10.1021/bi001372n 11284688

53. Kerr KM, Sauna ZE, Ambudkar SV. Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in Human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates. J Biol Chem. 2001;276: 8657–64. doi: 10.1074/jbc.M010044200 11121420

54. Urbatsch I, Sankaran B, Weber J, Senior A. P-Glycoprotein Is Stably Inhibited by Vanadate-Induced Trapping of Nucleotide at a Single Catalytic Site. J Biol Chem. 1995;270: 19383–19390. doi: 10.1074/jbc.270.33.19383 7642618

55. Szabo K, Welker E, Bakos E, Muller M, Roninson I, Varadi A, et al. Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1—Cooperation of the nucleotide binding domains. J Biol Chem. 1998;273: 10132–10138. doi: 10.1074/jbc.273.17.10132 9553060

56. Sarkadi B, Price EM, Boucher RC, Germann UA, Scarborough GA. Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J Biol Chem. 1992;267: 4854–8. 1347044

57. Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I. Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A. 1992;89: 8472–6. doi: 10.1073/pnas.89.18.8472 1356264

58. Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 1993;62: 385–427. doi: 10.1146/annurev.bi.62.070193.002125 8102521

59. Germann UA. P-glycoprotein—A mediator of multidrug resistance in tumour cells. Eur J Cancer. 1996;32: 927–944. doi: 10.1016/0959-8049(96)00057-3

60. Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice. Oncologist. 2003;8: 411–424. doi: 10.1634/theoncologist.8-5-411 14530494

61. Konig J, Muller F, Fromm MF. Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects. Pharmacol Rev. 2013;65: 944–966. doi: 10.1124/pr.113.007518 23686349

62. Ludescher C, Thaler J, Drach D, Drach J, Spitaler M, Gattringer C, et al. Detection of activity of P-glycoprotein in human tumour samples using rhodamine 123. Br J Haematol. 1992;82: 161–168. doi: 10.1111/j.1365-2141.1992.tb04608.x 1358171

63. Shapiro AB, Ling V. Extraction of Hoechst 33342 from the cytoplasmic leaflet of the plasma membrane by P-glycoprotein. Eur J Biochem. 1997;250: 122–9. doi: 10.1111/j.1432-1033.1997.00122.x 9431999

64. Shapiro AB, Ling V. Effect of quercetin on hoechst 33342 transport by purified and reconstituted p-glycoprotein. Biochem Pharmacol. 1997;53: 587–596. doi: 10.1016/s0006-2952(96)00826-x 9105411

65. Wolf MG, Hoefling M, Aponte-Santamaría C, Grubmüller H, Groenhof G. g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation. J Comput Chem. 2010;31: 2169–2174. doi: 10.1002/jcc.21507 20336801

66. Wolf MG, Hoefling M, Aponte-Santamaría C, Grubmüller H, Groenhof G. Corrigendum: g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation. J Comput Chem. 2016;37: 2038. doi: 10.1002/jcc.24386 27350658

67. Szöllősi D, Chiba P, Szakacs G, Stockner T. Conversion of chemical to mechanical energy by the nucleotide binding domains of ABCB1. Sci Rep. 2020;10: 2589. doi: 10.1038/s41598-020-59403-7 32054924

68. Szöllősi D, Szakács G, Chiba P, Stockner T. Dissecting the Forces that Dominate Dimerization of the Nucleotide Binding Domains of ABCB1. Biophys J. 2018;114: 331–342. doi: 10.1016/j.bpj.2017.11.022 29401431

69. Zolnerciks JK, Akkaya BG, Snippe M, Chiba P, Seelig A, Linton KJ. The Q loops of the human multidrug resistance transporter ABCB1 are necessary to couple drug binding to the ATP catalytic cycle. FASEB J. 2014;28: 4335–4346. doi: 10.1096/fj.13-245639 25016028

70. Sohail MI, Schmid D, Wlcek K, Spork M, Szakács G, Trauner M, et al. Molecular Mechanism of Taurocholate Transport by the Bile Salt Export Pump, an ABC Transporter Associated with Intrahepatic Cholestasis. Mol Pharmacol. 2017;92: 401–413. doi: 10.1124/mol.117.108688 28784620

71. Grossmann N, Vakkasoglu AS, Hulpke S, Abele R, Gaudet R, Tampé R. Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter. Nat Commun. 2014;5: 5419. doi: 10.1038/ncomms6419 25377891

72. Hohl M, Hurlimann LM, Bohm S, Schoppe J, Grutter MG, Bordignon E, et al. Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter. Proc Natl Acad Sci. 2014;111: 11025–11030. doi: 10.1073/pnas.1400485111 25030449

73. Wen P-C, Verhalen B, Wilkens S, Mchaourab HS, Tajkhorshid E. On the origin of large flexibility of P-glycoprotein in the inward-facing state. J Biol Chem. 2013;288: 19211–20. doi: 10.1074/jbc.M113.450114 23658020

74. Sharom FJ, Yu X, Chu JWK, Doige CA. Characterization of the ATPase activity of P-glycoprotein from multidrug-resistant Chinese hamster ovary cells. Biochem J. 1995;308: 381–390. doi: 10.1042/bj3080381 7772017

75. Verhalen B, Ernst S, Börsch M, Wilkens S. Dynamic ligand-induced conformational rearrangements in P-glycoprotein as probed by fluorescence resonance energy transfer spectroscopy. J Biol Chem. 2012;287: 1112–1127. doi: 10.1074/jbc.M111.301192 22086917

76. Prieß M, Göddeke H, Groenhof G, Schäfer LV. Molecular Mechanism of ATP Hydrolysis in an ABC Transporter. ACS Cent Sci. 2018;4: 1334–1343. doi: 10.1021/acscentsci.8b00369 30410971

77. Hsu W-L, Furuta T, Sakurai M. ATP Hydrolysis Mechanism in a Maltose Transporter Explored by QM/MM Metadynamics Simulation. J Phys Chem B. 2016;120: 11102–11112. doi: 10.1021/acs.jpcb.6b07332 27712074

78. Siarheyeva A, Liu R, Sharom FJ. Characterization of an asymmetric occluded state of P-glycoprotein with two bound nucleotides: implications for catalysis. J Biol Chem. 2010;285: 7575–7586. doi: 10.1074/jbc.M109.047290 20061384

79. Szakács G, Özvegy C, Bakos É, Sarkadi B, Váradi A. Transition-State Formation in ATPase-Negative Mutants of Human MDR1 Protein. Biochem Biophys Res Commun. 2000;276: 1314–1319. doi: 10.1006/bbrc.2000.3576 11027628

80. Furman C, Mehla J, Ananthaswamy N, Arya N, Kulesh B, Kovach I, et al. The deviant ATP-binding site of the multidrug efflux pump Pdr5 plays an active role in the transport cycle. J Biol Chem. 2013;288: 30420–30431. doi: 10.1074/jbc.M113.494682 24019526

81. Jones PM, George AM. Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record. Crit Rev Biochem Mol Biol. 2013;48: 39–50. doi: 10.3109/10409238.2012.735644 23131203

82. Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993;234: 779–815. doi: 10.1006/jmbi.1993.1626 8254673

83. Shen M, Sali A. Statistical potential for assessment and prediction of protein structures. Protein Sci. 2006;15: 2507–2524. doi: 10.1110/ps.062416606 17075131

84. Stockner T, de Vries SJ, Bonvin AMJJ, Ecker GF, Chiba P. Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains. FEBS J. 2009;276: 964–972. doi: 10.1111/j.1742-4658.2008.06832.x 19215299

85. Berger O, Edholm O, Jahnig F, Jähnig F. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J. 1997;72: 2002–13. doi: 10.1016/S0006-3495(97)78845-3 9129804

86. Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins Struct Funct Bioinforma. 2010;78: 1950–1958. doi: 10.1002/prot.22711 20408171

87. Meagher KL, Redman LT, Carlson HA. Development of polyphosphate parameters for use with the AMBER force field. J Comput Chem. 2003;24: 1016–1025. doi: 10.1002/jcc.10262 12759902

88. Bussi G, Donadio D, Parrinello M. Canonical sampling through velocity rescaling. J Chem Phys. 2007;126: 014101. doi: 10.1063/1.2408420 17212484

89. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J Chem Phys. 1984;81: 3684–3690. doi: 10.1063/1.448118

90. Darden T, York D, Pedersen L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. J Chem Phys. 1993;98: 10089–92. doi: 10.1063/1.464397

91. Miyamoto S, Kollman PA. Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models. J Comput Chem. 1992;13: 952–962. doi: 10.1002/jcc.540130805

92. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM. LINCS: A linear constraint solver for molecular simulations. J Comput Chem. 1997;18: 1463–1472. doi: 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H

93. Szollosi J, Horejsi V, Bene L, Angelisova P, Damjanovich S. Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. J Immunol. 1996;157: 2939–2946. 8816400

94. Kolacsek O, Krizsik V, Schamberger A, Erdei Z, Apati A, Varady G, et al. Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers. Mob Dna. 2011;2: 5. doi: 10.1186/1759-8753-2-5 21371313

95. Kolacsek O, Krízsik V, Schamberger A, Erdei Z, Apáti A, Várady G, et al. Correction: Reliable transgene-independent method for determining sleeping beauty transposon copy numbers. Mob DNA. 2013;4: 11. doi: 10.1186/1759-8753-4-11 23497459

96. Mates L, Chuah MKL, Belay E, Jerchow B, Manoj N, Acosta-Sanchez A, et al. Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates. Nat Genet. 2009;41: 753–761. doi: 10.1038/ng.343 19412179

97. Izsvak Z, Ivics Z, Plasterk RH. Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates. J Mol Biol. 2000;302: 93–102. doi: 10.1006/jmbi.2000.4047 10964563

98. Trencsenyi G, Kertesz I, Krasznai ZT, Mate G, Szaloki G, Judit PS, et al. 2 ‘[F-18]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function. Eur J Pharm Sci. 2015;74: 27–35. doi: 10.1016/j.ejps.2015.03.026 25857708

99. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193: 265–275. 14907713

100. Tarapcsak S, Szaloki G, Telbisz A, Gyoengy Z, Matuz K, Csosz E, et al. Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein. Sci Rep. 2017;7: 41376. doi: 10.1038/srep41376 28145501

101. Krasznai ZT, Trencsenyi G, Krasznai Z, Mikecz P, Nizsaloczki E, Szaloki G, et al. (18)FDG a PET tumor diagnostic tracer is not a substrate of the ABC transporter P-glycoprotein. Eur J Pharm Sci. 2014;64: 1–8. doi: 10.1016/j.ejps.2014.08.002 25149126

102. Hollo Z, Homolya L, Davis C, Sarkadi B. Calcein Accumulation as a Fluorometric Functional Assay of the Multidrug Transporter. Biochim Biophys Acta-Biomembr. 1994;1191: 384–388. doi: 10.1016/0005-2736(94)90190-2


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se