Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels

Zangerl-Plessl, Eva-Maria; Lee, Sun-Joo; Maksaev, Grigory; Bernsteiner, Harald; Ren, Feifei; Yuan, Peng; Stary-Weinzinger, Anna; Nichols, Colin G.

doi:10.1085/jgp.201912422

Title: Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels

Journal Article · Tue Nov 19 00:00:00 EST 2019 · Journal of General Physiology

DOI:https://doi.org/10.1085/jgp.201912422· OSTI ID:1574555

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^[2]; Bernsteiner, Harald ^[1]; Ren, Feifei ^[2]; Yuan, Peng ^[2];

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Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
Department of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO

Potassium ion conduction through open potassium channels is essential to control of membrane potentials in all cells. To elucidate the open conformation and hence the mechanism of K ⁺ ion conduction in the classic inward rectifier Kir2.2, we introduced a negative charge (G178D) at the crossing point of the inner helix bundle, the location of ligand-dependent gating. This “forced open” mutation generated channels that were active even in the complete absence of phosphatidylinositol-4,5-bisphosphate (PIP ₂ ), an otherwise essential ligand for Kir channel opening. Crystal structures were obtained at a resolution of 3.6 Å without PIP ₂ bound, or 2.8 Å in complex with PIP ₂ . The latter revealed a slight widening at the helix bundle crossing (HBC) through backbone movement. MD simulations showed that subsequent spontaneous wetting of the pore through the HBC gate region allowed K ⁺ ion movement across the HBC and conduction through the channel. Further simulations reveal atomistic details of the opening process and highlight the role of pore-lining acidic residues in K ⁺ conduction through Kir2 channels.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Austrian Science Fund (FWF)

Grant/Contract Number:: AC02-06CH11357; AC02-06CH1135; GM103403; RR029205; OD021527; HL140024; W1232; I-2101-B26

OSTI ID:: 1574555

Alternate ID(s):: OSTI ID: 1581821

Journal Information:: Journal of General Physiology, Journal Name: Journal of General Physiology; ISSN 0022-1295

Country of Publication:: United States

Language:: English

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Cited by: 16 works

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References (73)

Crystal Structure of the Mammalian GIRK2 K+ Channel and Gating Regulation by G Proteins, PIP2, and Sodium Whorton, Matthew R.; MacKinnon, Roderick Cell, Vol. 147, Issue 1 https://doi.org/10.1016/j.cell.2011.07.046	journal	September 2011
Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels Linder, Tobias; Wang, Shizhen; Zangerl-Plessl, Eva-Maria Journal of Chemical Information and Modeling, Vol. 55, Issue 4 https://doi.org/10.1021/acs.jcim.5b00010	journal	March 2015
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
Filter Flexibility and Distortion in a Bacterial Inward Rectifier K+ Channel: Simulation Studies of KirBac1.1 Domene, Carmen; Grottesi, Alessandro; Sansom, Mark S. P. Biophysical Journal, Vol. 87, Issue 1 https://doi.org/10.1529/biophysj.104.039917	journal	July 2004
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
Bendix: intuitive helix geometry analysis and abstraction Dahl, A. C. E.; Chavent, M.; Sansom, M. S. P. Bioinformatics, Vol. 28, Issue 16 https://doi.org/10.1093/bioinformatics/bts357	journal	June 2012
Structural dynamics of potassium-channel gating revealed by single-molecule FRET Wang, Shizhen; Vafabakhsh, Reza; Borschel, William F. Nature Structural & Molecular Biology, Vol. 23, Issue 1 https://doi.org/10.1038/nsmb.3138	journal	December 2015
Mechanism of Voltage Gating in Potassium Channels Jensen, M. O.; Jogini, V.; Borhani, D. W. Science, Vol. 336, Issue 6078 https://doi.org/10.1126/science.1216533	journal	April 2012
Ion permeation in K+ channels occurs by direct Coulomb knock-on Kopfer, D. A.; Song, C.; Gruene, T. Science, Vol. 346, Issue 6207 https://doi.org/10.1126/science.1254840	journal	October 2014
Anomalous X-ray diffraction studies of ion transport in K+ channels Langan, Patricia S.; Vandavasi, Venu Gopal; Weiss, Kevin L. Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-06957-w	journal	October 2018
X-ray structure of the mammalian GIRK2–βγ G-protein complex Whorton, Matthew R.; MacKinnon, Roderick Nature, Vol. 498, Issue 7453 https://doi.org/10.1038/nature12241	journal	June 2013
Atypical mechanism of conduction in potassium channels Furini, S.; Domene, C. Proceedings of the National Academy of Sciences, Vol. 106, Issue 38 https://doi.org/10.1073/pnas.0903226106	journal	September 2009
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel. Schönherr, R.; Heinemann, S. H. The Journal of Physiology, Vol. 493, Issue 3 https://doi.org/10.1113/jphysiol.1996.sp021410	journal	June 1996
Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids Lee, Sun-Joo; Ren, Feifei; Zangerl-Plessl, Eva-Maria The Journal of General Physiology, Vol. 148, Issue 3 https://doi.org/10.1085/jgp.201611616	journal	August 2016
Physical determinants of strong voltage sensitivity of K+ channel block Xu, Yanping; Shin, Hyeon-Gyu; Szép, Szilvia Nature Structural & Molecular Biology, Vol. 16, Issue 12 https://doi.org/10.1038/nsmb.1717	journal	November 2009
Energetics of ion conduction through the K+ channel Bernèche, Simon; Roux, Benoît Nature, Vol. 414, Issue 6859 https://doi.org/10.1038/35102067	journal	November 2001
HOLLOW: Generating Accurate Representations of Channel and Interior Surfaces in Molecular Structures Ho, Bosco K.; Gruswitz, Franz BMC Structural Biology, Vol. 8, Issue 1 https://doi.org/10.1186/1472-6807-8-49	journal	January 2008
Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating Bavro, Vassiliy N.; De Zorzi, Rita; Schmidt, Matthias R. Nature Structural & Molecular Biology, Vol. 19, Issue 2 https://doi.org/10.1038/nsmb.2208	journal	January 2012
Automatic atom type and bond type perception in molecular mechanical calculations Wang, Junmei; Wang, Wei; Kollman, Peter A. Journal of Molecular Graphics and Modelling, Vol. 25, Issue 2 https://doi.org/10.1016/j.jmgm.2005.12.005	journal	October 2006
A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel Aryal, Prafulla; Abd-Wahab, Firdaus; Bucci, Giovanna Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5377	journal	July 2014
Molecular Dynamics Simulations of Inwardly Rectifying (Kir) Potassium Channels: A Comparative Study ^† Haider, Shozeb; Khalid, Syma; Tucker, Stephen J. Biochemistry, Vol. 46, Issue 12 https://doi.org/10.1021/bi062210f	journal	March 2007
Crystal structure of a Kir3.1-prokaryotic Kir channel chimera Nishida, Motohiko; Cadene, Martine; Chait, Brian T. The EMBO Journal, Vol. 26, Issue 17 https://doi.org/10.1038/sj.emboj.7601828	journal	August 2007
Coupled K ⁺ –Water Flux through the HERG Potassium Channel Measured by an Osmotic Pulse Method Ando, Hiroyuki; Kuno, Miyuki; Shimizu, Hirofumi The Journal of General Physiology, Vol. 126, Issue 5 https://doi.org/10.1085/jgp.200509377	journal	October 2005
Dual-Mode Phospholipid Regulation of Human Inward Rectifying Potassium Channels Cheng, Wayland W. L.; D'Avanzo, Nazzareno; Doyle, Declan A. Biophysical Journal, Vol. 100, Issue 3 https://doi.org/10.1016/j.bpj.2010.12.3724	journal	February 2011
CHAP: A Versatile Tool for the Structural and Functional Annotation of Ion Channel Pores Klesse, Gianni; Rao, Shanlin; Sansom, Mark S. P. Journal of Molecular Biology, Vol. 431, Issue 17 https://doi.org/10.1016/j.jmb.2019.06.003	journal	August 2019
GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers Abraham, Mark James; Murtola, Teemu; Schulz, Roland SoftwareX, Vol. 1-2 https://doi.org/10.1016/j.softx.2015.06.001	journal	September 2015
Bayesian model aggregation for ensemble-based estimates of protein pK _a values : BMA for Protein p Gosink, Luke J.; Hogan, Emilie A.; Pulsipher, Trenton C. Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 3 https://doi.org/10.1002/prot.24390	journal	October 2013
An approach to multi-copy search in molecular replacement Vagin, Alexei; Teplyakov, Alexei Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 12 https://doi.org/10.1107/S0907444900013780	journal	December 2000
Locale and chemistry of spermine binding in the archetypal inward rectifier Kir2.1 Kurata, Harley T.; Zhu, Emily A.; Nichols, Colin G. The Journal of General Physiology, Vol. 135, Issue 5 https://doi.org/10.1085/jgp.200910253	journal	April 2010
Cryo-EM Structure of the Open Human Ether-à-go-go -Related K + Channel hERG Wang, Weiwei; MacKinnon, Roderick Cell, Vol. 169, Issue 3 https://doi.org/10.1016/j.cell.2017.03.048	journal	April 2017
Comparison of multiple Amber force fields and development of improved protein backbone parameters Hornak, Viktor; Abel, Robert; Okur, Asim Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 3 https://doi.org/10.1002/prot.21123	journal	November 2006
Molecular simulation studies of hydrophobic gating in nanopores and ion channels Trick, Jemma L.; Aryal, Prafulla; Tucker, Stephen J. Biochemical Society Transactions, Vol. 43, Issue 2 https://doi.org/10.1042/BST20140256	journal	April 2015
The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity Doyle, D. A. Science, Vol. 280, Issue 5360 https://doi.org/10.1126/science.280.5360.69	journal	April 1998
Membrane Protein Simulations Using AMBER Force Field and Berger Lipid Parameters Cordomí, Arnau; Caltabiano, Gianluigi; Pardo, Leonardo Journal of Chemical Theory and Computation, Vol. 8, Issue 3 https://doi.org/10.1021/ct200491c	journal	February 2012
Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating Martin, Gregory M.; Yoshioka, Craig; Rex, Emily A. eLife, Vol. 6 https://doi.org/10.7554/eLife.24149	journal	January 2017
Secondary anionic phospholipid binding site and gating mechanism in Kir2.1 inward rectifier channels Lee, Sun-Joo; Wang, Shizhen; Borschel, William Nature Communications, Vol. 4, Issue 1 https://doi.org/10.1038/ncomms3786	journal	November 2013
Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels Kopec, Wojciech; Köpfer, David A.; Vickery, Owen N. Nature Chemistry, Vol. 10, Issue 8 https://doi.org/10.1038/s41557-018-0105-9	journal	July 2018
Inward Rectifier Potassium Channels Nichols, C. G.; Lopatin, A. N. Annual Review of Physiology, Vol. 59, Issue 1 https://doi.org/10.1146/annurev.physiol.59.1.171	journal	October 1997
A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification Brelidze, T. I.; Niu, X.; Magleby, K. L. Proceedings of the National Academy of Sciences, Vol. 100, Issue 15 https://doi.org/10.1073/pnas.1532257100	journal	July 2003
Ion permeation mechanism of the potassium channel Åqvist, Johan; Luzhkov, Victor Nature, Vol. 404, Issue 6780 https://doi.org/10.1038/35009114	journal	April 2000
Crystal Structure of the Eukaryotic Strong Inward-Rectifier K+ Channel Kir2.2 at 3.1 A Resolution Tao, X.; Avalos, J. L.; Chen, J. Science, Vol. 326, Issue 5960 https://doi.org/10.1126/science.1180310	journal	December 2009
Canonical sampling through velocity rescaling Bussi, Giovanni; Donadio, Davide; Parrinello, Michele The Journal of Chemical Physics, Vol. 126, Issue 1 https://doi.org/10.1063/1.2408420	journal	January 2007
Hydrophobic Gating in Ion Channels Aryal, Prafulla; Sansom, Mark S. P.; Tucker, Stephen J. Journal of Molecular Biology, Vol. 427, Issue 1 https://doi.org/10.1016/j.jmb.2014.07.030	journal	January 2015
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems Darden, Tom; York, Darrin; Pedersen, Lee The Journal of Chemical Physics, Vol. 98, Issue 12 https://doi.org/10.1063/1.464397	journal	June 1993
Ligand-induced Closure of Inward Rectifier Kir6.2 Channels Traps Spermine in the Pore Phillips, L. Revell; Nichols, Colin G. The Journal of General Physiology, Vol. 122, Issue 6 https://doi.org/10.1085/jgp.200308953	journal	November 2003
Potassium channels in the heart: structure, function and regulation: Potassium channels in the heart Grandi, Eleonora; Sanguinetti, Michael C.; Bartos, Daniel C. The Journal of Physiology, Vol. 595, Issue 7 https://doi.org/10.1113/JP272864	journal	November 2016
HOLE: A program for the analysis of the pore dimensions of ion channel structural models Smart, Oliver S.; Neduvelil, Joseph G.; Wang, Xiaonan Journal of Molecular Graphics, Vol. 14, Issue 6 https://doi.org/10.1016/S0263-7855(97)00009-X	journal	December 1996
Principles of conduction and hydrophobic gating in K+ channels Jensen, M. O.; Borhani, D. W.; Lindorff-Larsen, K. Proceedings of the National Academy of Sciences, Vol. 107, Issue 13 https://doi.org/10.1073/pnas.0911691107	journal	March 2010
Water Permeation Across Biological Membranes: Mechanism and Dynamics of Aquaporin-1 and GlpF de Groot, Bert L.; Grubmüller, Helmut Science, Vol. 294, Issue 5550 https://doi.org/10.1126/science.1066115	journal	December 2001
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Identification of the Conformational transition pathway in PIP2 Opening Kir Channels Li, Junwei; Lü, Shouqin; Liu, Yuzhi Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep11289	journal	June 2015
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment Long, Stephen B.; Tao, Xiao; Campbell, Ernest B. Nature, Vol. 450, Issue 7168 https://doi.org/10.1038/nature06265	journal	November 2007
Regulation of Cardiac Na+,Ca2+ Exchange and KATP Potassium Channels by PIP2 Hilgemann, D. W.; Ball, R. Science, Vol. 273, Issue 5277 https://doi.org/10.1126/science.273.5277.956	journal	August 1996
SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modeling Guex, Nicolas; Peitsch, Manuel C. Electrophoresis, Vol. 18, Issue 15, p. 2714-2723 https://doi.org/10.1002/elps.1150181505	journal	January 1997
Electrostatic Tuning of Ion Conductance in Potassium Channels Nimigean, Crina M.; Chappie, Joshua S.; Miller, Christopher Biochemistry, Vol. 42, Issue 31 https://doi.org/10.1021/bi0348720	journal	August 2003
Functional Roles of Charged Amino Acid Residues on the Wall of the Cytoplasmic Pore of Kir2.1 Fujiwara, Yuichiro; Kubo, Yoshihiro The Journal of General Physiology, Vol. 127, Issue 4 https://doi.org/10.1085/jgp.200509434	journal	March 2006
ATP Interaction with the Open State of the KATP Channel Enkvetchakul, D.; Loussouarn, G.; Makhina, E. Biophysical Journal, Vol. 80, Issue 2 https://doi.org/10.1016/S0006-3495(01)76051-1	journal	February 2001
Constitutive Activation of the Shaker Kv Channel Sukhareva, Manana; Hackos, David H.; Swartz, Kenton J. The Journal of General Physiology, Vol. 122, Issue 5 https://doi.org/10.1085/jgp.200308905	journal	October 2003
Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification Lopatin, Anatoli N.; Makhina, Elena N.; Nichols, Colin G. Nature, Vol. 372, Issue 6504 https://doi.org/10.1038/372366a0	journal	November 1994
Microinjection Technique: Routine System for Characterization of Microcapillaries by Bubble Pressure Measurement Schnorf, Martin; Potrykus, Ingo; Neuhaus, Gunther Experimental Cell Research, Vol. 210, Issue 2 https://doi.org/10.1006/excr.1994.1038	journal	February 1994
Structural rearrangements underlying ligand-gating in Kir channels Wang, Shizhen; Lee, Sun-Joo; Heyman, Sarah Nature Communications, Vol. 3, Issue 1 https://doi.org/10.1038/ncomms1625	journal	January 2012
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2 Hansen, Scott B.; Tao, Xiao; MacKinnon, Roderick Nature, Vol. 477, Issue 7365 https://doi.org/10.1038/nature10370	journal	August 2011
Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations Joung, In Suk; Cheatham, Thomas E. The Journal of Physical Chemistry B, Vol. 112, Issue 30 https://doi.org/10.1021/jp8001614	journal	July 2008
Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels Díaz-Franulic, Ignacio; Sepúlveda, Romina V.; Navarro-Quezada, Nieves The Journal of General Physiology, Vol. 146, Issue 2 https://doi.org/10.1085/jgp.201411353	journal	July 2015
Highly Perturbed pKa Values in the Unfolded State of Hen Egg White Lysozyme Bradley, John; O'Meara, Fergal; Farrell, Damien Biophysical Journal, Vol. 102, Issue 7 https://doi.org/10.1016/j.bpj.2012.02.048	journal	April 2012
Pore size matters for potassium channel conductance Naranjo, David; Moldenhauer, Hans; Pincuntureo, Matías The Journal of General Physiology, Vol. 148, Issue 4 https://doi.org/10.1085/jgp.201611625	journal	September 2016
Potassium channel selectivity filter dynamics revealed by single-molecule FRET Wang, Shizhen; Lee, Sun-Joo; Maksaev, Grigory Nature Chemical Biology, Vol. 15, Issue 4 https://doi.org/10.1038/s41589-019-0240-7	journal	March 2019
Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles Hibino, Hiroshi; Inanobe, Atsushi; Furutani, Kazuharu Physiological Reviews, Vol. 90, Issue 1 https://doi.org/10.1152/physrev.00021.2009	journal	January 2010
The missing term in effective pair potentials Berendsen, H. J. C.; Grigera, J. R.; Straatsma, T. P. The Journal of Physical Chemistry, Vol. 91, Issue 24 https://doi.org/10.1021/j100308a038	journal	November 1987
Conduction through a narrow inward-rectifier K ⁺ channel pore Bernsteiner, Harald; Zangerl-Plessl, Eva-Maria; Chen, Xingyu The Journal of General Physiology, Vol. 151, Issue 10 https://doi.org/10.1085/jgp.201912359	journal	September 2019
Direct and Specific Activation of Human Inward Rectifier K ⁺ Channels by Membrane Phosphatidylinositol 4,5-Bisphosphate D'Avanzo, Nazzareno; Cheng, Wayland W. L.; Doyle, Declan A. Journal of Biological Chemistry, Vol. 285, Issue 48 https://doi.org/10.1074/jbc.C110.186692	journal	October 2010
Mutations within the P-Loop of Kir6.2 Modulate the Intraburst Kinetics of the Atp-Sensitive Potassium Channel Proks, Peter; Capener, Charlotte E.; Jones, Phillippa The Journal of General Physiology, Vol. 118, Issue 4 https://doi.org/10.1085/jgp.118.4.341	journal	September 2001
Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel Long, S. B. Science, Vol. 309, Issue 5736 https://doi.org/10.1126/science.1116269	journal	August 2005

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Title: Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels

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