Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations

Proteins: Structure, Function and Bioinformatics

Volumn 78, Issue 14, 2010, Pages 2922-2934

  Subbotina, Julia ^a   Yarov Yarovoy, Vladimir ^b   Lees Miller, James ^c   Durdagi, Serdar ^a   Guo, Jiqing ^c   Duff, Henry J ^c   Noskov, Sergei Yu ^a  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c LIBIN CARDIOVASCULAR INSTITUTE OF ALBERTA   (Canada)

Author keywords

De novo design; HERG1 channel; Mechanism; Proteindrug interactions

Indexed keywords

DOFETILIDE; N [2 [[N [3 (4 CHLOROPHENYL) 2 PROPENYL] N METHYLAMINO]METHYL]PHENYL] N (2 HYDROXYETHYL) 4 METHOXYBENZENESULFONAMIDE; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL HERG1; POTASSIUM CHANNEL KV1.2; POTASSIUM CHANNEL KV11.1; POTASSIUM CHANNEL KV2.1; POTASSIUM CHANNEL KVAP; SHAB POTASSIUM CHANNEL; UNCLASSIFIED DRUG; VOLTAGE GATED POTASSIUM CHANNEL;

ARTICLE; CONTROLLED STUDY; ELECTRIC POTENTIAL; ELECTROPHYSIOLOGY; MEMBRANE MODEL; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MUTAGENESIS; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STRUCTURE; SEQUENCE ALIGNMENT; SIMULATION;

EID: 77957963878     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.22815     Document Type: Article

References (65)

1. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A Molecular-basis for cardiac-arrhythmia: Herg mutations cause long Qt syndrome. Cell 1995;80:795-803.
2. Tseng GN. I(Kr): the hERG channel. J Mol Cell Cardiol 2001;33:835-849.
3. Vandenberg JI, Walker BD, Campbell TJ. HERG K+ channels: friend and foe. Trends Pharm Sci 2001;22:240-246.
4. Splawski I, Shen JX, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT. Spectrum of mutations in long-QT syndrome genes KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000;102:1178-1185.
5. Witchel HJ, Hancox JC. Familial and acquired long QT syndrome and the cardiac rapid delayed rectifier potassium current. Clin Exp Pharm Physiol 2000;27:753-766.
6. Saenen JB, Paulussen ADC, Jongbloed RJ, Marcelis CL, Gilissen RAHJ, Aerssens J, Snyders DJ, Raes AL. A single hERG mutation underlying a spectrum of acquired and congenital long QT syndrome phenotypes. J Mol Cell Cardiol 2007;43:63-72.
7. Seebohm G, Strutz-Seebohm N, Ureche ON, Henrion U, Baltaev R, Mack AF, Korniychuk G, Steinke K, Tapken D, Pfeufer A, Kaab S, Bucci C, Attali B, Merot J, Tavare JM, Hoppe UC, Sanguinetti MC, Lang F. Long QT syndrome-associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of I-Ks channels. Circ Res 2008;103:1451-U1217.
8. Huang FD, Chen J, Lin M, Keating MT, Sanguinetti MC. Long-QT syndrome-associated missense mutations in the pore helix of the HERG potassium channel. Circulation 2001;104:1071-1075.
9. Lees-Miller JP, Duan YJ, Teng GQ, Thorstad K, Duff HJ. Novel gain-of-function mechanism in K+ channel-related long-QT syndrome: altered gating and selectivity in the HERG1 N629D mutant. Circ Res 2000;86:507-513.
10. Teng GQ, Lees-Miller JP, Duan YJ, Li BT, Li P, Duff HJ. [K+](o)-dependent change in conformation of the HERG1 long QT mutation N629D channel results in partial reversal of the in vitro disease phenotype. Cardiovasc Res 2003;57:642-650.
11. Sanguinetti MC, Mitcheson JS. Predicting drug-hERG channel interactions that cause acquired long QT syndrome. Trens Pharm Sci 2005;26:119-124.
12. Perry M, de GM, Helliwell R, Leishman D, Tristani-Firouzi M, Sanguinetti MC, Mitcheson J. Structural determinants of HERG channel block by clofilium and ibutilide. Mol Pharmacol 2004;66:240-249.
13. Stansfeld PJ, Gedeck P, Gosling M, Cox B, Mitcheson JS, Sutcliffe MJ. Drug block of the hERG potassium channel: insight from modeling. Proteins 2007;68:568-580.
14. Nattel S, Carlsson L. Innovative approaches to anti-arrhythmic drug therapy. Nature Rev Drug Disc 2006;5:1034-1049.
15. Sanguinetti MC, Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature 2006;440:463-469.
16. Stary A, Wacker SJ, Boukharta L, Zachariae U, Karimi-Nejad Y, Aqvist J, Vriend G, de Groot BL. Toward a consensus model of the hERG potassium channel. Chem Med Chem 2010;5:455-467.
17. Lees-Miller JP, Subbotina JO, Guo J, Yarov-Yarovoy V, Noskov SY, Duff HJ. Interactions of H562 in the S5 helix with T618 and S621 in the pore helix are important determinants of hERG1 potassium channel structure and function. Biophys J 2009;96:3600-3610.
18. Osterberg F, Aqvist J. Exploring blocker binding to a homology model of the open hERG K+ channel using docking and molecular dynamics methods. FEBS Lett 2005;579:2939-2944.
19. Kutteh R, Vandenberg JI, Kuyucak S. Molecular dynamics and continuum electrostatics studies of inactivation in the HERG potassium channel. J Phys Chem B 2007;111:1090-1098.
20. Ju P, Pages G, Riek RP, Chen PC, Torres AM, Bansal PS, Kuyucak S, Kuchel PW, Vandenberg JI. The pore domain outer helix contributes to both activation and inactivation of the HERG K+ channel. J Biol Chem 2009;284:1000-1008.
21. Tseng GN, Sonawane KD, Korolkova YV, Zhang M, Liu J, Grishin EV, Guy HR. Probing the outer mouth structure of the HERG channel with peptide toxin footprinting and molecular modeling. Biophys J 2007;92:3524-3540.
22. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG. Clustal W and clustal X version 2.0. Bioinformatics 2007;23:2947-2948.
23. Elofsson A, von Heijne G. Membrane protein structure: prediction versus reality. Annu Rev Biochem 2007;76:125-140.
24. Yarov-Yarovoy V, Schonbrun J, Baker D. Multipass membrane protein structure prediction using Rosetta. Proteins 2006;62:1010-1025.
25. Barth P, Wallner B, Baker D. Prediction of membrane protein structures with complex topologies using limited constraints. Proc Natl Acad Sci USA 2009;106:1409-1414.
26. Long SB, Campbell EB, MacKinnon R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 2005;309:897-903.
27. Long SB, Campbell EB, MacKinnon R. Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 2005;309:903-908.
28. Long SB, Tao X, Campbell EB, MacKinnon R. Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 2007;450:376-U373.
29. Yarov-Yarovoy V, Baker D, Catterall WA. Voltage sensor conformations in the open and closed states in ROSETTA structural models of K+ channels. Proc Natl Acad Sci USA 2006;103:7292-7297.
30. Pathak MM, Yarov-Yarovoy V, Agarwal G, Roux B, Barth P, Kohout S, Tombola F, Isacoff EY. Closing in on the resting state of the shaker K+ channel. Neuron 2007;56:124-140.
31. Noskov SY, Berneche S, Roux B. Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands. Nature 2004;431:830-834.
32. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JA, Montgomery JR Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, and Pople JA. Gaussian 03 RC. Wallingford CT: Gaussian, Inc; 2004.
33. Morris GM, Goodsell DS, Huey R, Olson AJ. Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4. J Comp-Aid Mol Des 1996;10:293-304.
34. Jones G, Willett P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997;267:727-748.
35. Bjelkmar P, Niemela PS, Vattulainen I, Lindahl E. Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel. PLOS Comp Biol 2009;5:e1000289.
36. Bezanilla F. Voltage sensor: function and structure. J Phys Sci 2009;59:90.
37. Villalba-Galea CA, Sandtner W, Starace DM, Bezanilla F. S4-based voltage sensors have three major conformations. Proc Natl Acad Sci USA 2008;105:17600-17607.
38. Chakrapani S, Sompornpisut P, Intharathep P, Roux B, Perozo E. The activated state of a sodium channel voltage sensor in a membrane environment. Proc Natl Acad Sci USA 2010;107:5435-5440.
39. Jogini V, Roux B. Dynamics of the Kv1.2 voltage-gated K+ channel in a membrane environment. Biophys J 2007;93:3070-3082.
40. Khalili-Araghi F, Tajkhorshid E, Schulten K. Dynamics of K+ ion conduction through Kv1.2. Biophys J 2007:616A-619A.
41. Freites JA, Tobias DJ, White SH. A voltage-sensor water pore. Biophys J 2006;91:L90-L92.
42. Zhang M, Liu J, Tseng GN. Gating charges in the activation and inactivation processes of the hERG channel. J Gen Physiol 2004;124:703-718.
43. Zhang M, Liu J, Jiang M, Wu DM, Sonawane K, Guy HR, Tseng GN. Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel. J Membr Biol 2005;207:169-181.
44. Liu J, Zhang M, Jiang M, Tseng GN. Negative charges in the transmembrane domains of the HERG K channel are involved in the activation-and deactivation-gating processes. J Gen Physiol 2003;121:599-614.
45. Fernandez D, Ghanta A, Kinard KI, Sanguinetti MC. Molecular mapping of a site for Cd2+-induced modification of human ethera-go-go-related gene (hERG) channel activation. J Phys London 2005;567:737-755.
46. Subbiah RN, Kondo M, Campbell TJ, Vandenberg JI. Tryptophan scanning mutagenesis of the HERG K+ channel: the S4 domain is loosely packed and likely to be lipid exposed. J Phys London 2005;569:367-379.
47. Subbiah RN, Clarke CE, Smith DJ, Zhao J, Campbell TJ, Vandenberg JI. Molecular basis of slow activation of the human ether-ago-go related gene potassium channel. J Physiol 2004;558:417-431.
48. Subbiah RN, Clarke CE, Smith DJ, Zhao JT, Vandenberg JI, Campbell TJ. Alteration of voltage-dependence and activation kinetics of the HERG potassium channel by mutations in the S4 sequence. Biophys J 2004;86:541a-541a.
49. Piper DR, Rupp J, Sachse FB, Sanguinetti MC, Tristani-Firouzi M. Cooperative interactions between R531 and acidic residues in the voltage sensing module of hERG1 channels. Cell Physiol Biochem 2008;21:37-46.
50. Torres AM, Bansal PS, Sunde M, Clarke CE, Bursill JA, Smith DJ, Bauskin A, Breit SN, Campbell TJ, Alewood PF, Kuchel PW, Vandenberg JI. Structure of the HERG K+ channel S5P extracellular linker: role of an amphipathic alpha-helix in C-type inactivation. J Biol Chem 2003;278:42136-42148.
51. Jiang M, Zhang M, Maslennikov IV, Liu J, Wu DM, Korolkova YV, Arseniev AS, Grishin EV, Tseng GN. Dynamic conformational changes of extracellular S5-P linkers in the hERG channel. J Physiol 2005;569:75-89.
52. Stansfeld PJ, Grottesi A, Sands ZA, Sansom MS, Gedeck P, Gosling M, Cox B, Stanfield PR, Mitcheson JS, Sutcliffe MJ. Insight into the mechanism of inactivation and pH sensitivity in potassium channels from molecular dynamics simulations. Biochemistry 2008;47: 7414-7422.
53. Ander M, Luzhkov VB, Aqvist J. Ligand binding to the voltage-gated Kv1.5 potassium channel in the open state-docking and computer simulations of a homology model. Biophys J 2008;94:820-831.
54. Perry M, de Groot MJ, Helliwell R, Leishman D, Tristani-Firouzi M, Sanguinetti MC, Mitcheson J. Structural determinants of HERG channel block by clofilium and ibutilide. Mol Pharmacol 2004;66:240-249.
55. Lees-Miller JP, Duan YJ, Teng GQ, Duff HJ. Molecular determinant of high-affinity dofetilide binding to HERG1 expressed in Xenopus oocytes: involvement of S6 sites. Mol Pharmacol 2000;57:367-374.
56. Seebohm G, Chen J, Strutz N, Culberson C, Lerche C, Sanguinetti MC. Molecular determinants of KCNQ1 channel block by a benzodiazepine. Mol Pharmacol 2003;64:70-77.
57. Mitcheson J, Perry M, Stansfeld P, Sanguinetti MC, Witchel H, Hancox J. Structural determinants for high-affinity block of hERG potassium channels. Novartis Found Symp 2005;266:136-150.
58. Aqvist J, Luzhkov VB, Brandsdal BO. Ligand binding affinities from MD simulations. Acc Chem Res 2002;35:358-365.
59. Fernandez D, Sargent J, Sachse FB, Sanguinetti MC. Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid. Mol Pharmacol 2008;73:1159-1167.
60. Casis O, Olesen SP, Sanguinetti MC. Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol Pharmacol 2006;69:658-665
61. Seebohm G. Activators of cation channels: potential in treatment of channelopathies. Mol Pharmacol 2005;67:585-588.
62. Mobley DL, Dill KA. Binding of small-molecule ligands to proteins: "What You See" Is Not Always "What You Get". Structure 2009;17:489-498.
63. Noskov SY. Molecular mechanism of substrate specificity in the bacterial neutral amino acid transporter LeuT. Proteins 2008;73:851-863.
64. Deng YQ, Roux B. Computations of standard binding free energies with molecular dynamics simulations. J Phys Chem B 2009;113:2234-2246.
65. Durdagi S, Subbotina J, Lees-Miller J, Guo J, Duff HJ, Noskov, SY. Insights into the molecular mechanism of hERG1 channel activation and blockade by drugs. Curr Med Chem 2010;17:1-19.