Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids

Lee, Sun-Joo; Ren, Feifei; Zangerl-Plessl, Eva-Maria; Heyman, Sarah; Stary-Weinzinger, Anna; Yuan, Peng; Nichols, Colin G.

doi:10.1085/jgp.201611616

Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids

Journal Article · Mon Aug 15 04:00:00 EDT 2016 · Journal of General Physiology

DOI:https://doi.org/10.1085/jgp.201611616· OSTI ID:1351381

Lee, Sun-Joo; Ren, Feifei; Zangerl-Plessl, Eva-Maria; Heyman, Sarah; ; Yuan, Peng; Nichols, Colin G.

Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP₂) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL^-) with a distinct second site is required for high PIP₂sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP₂sensitivity, even in the absence of PL^-. Furthermore, high-resolution x-ray crystal structures of Kir2.2[K62W], with or without added PIP₂(2.8- and 2.0-Å resolution, respectively), reveal tight tethering of the C-terminal domain (CTD) to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating in which PL^-binding at the second site pulls the CTD toward the membrane, inducing the formation of the high-affinity primary PIP₂site and explaining the positive allostery between PL^-binding and PIP₂sensitivity.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIH; AHA

OSTI ID:: 1351381

Journal Information:: Journal of General Physiology, Journal Name: Journal of General Physiology Journal Issue: 3 Vol. 148; ISSN 0022-1295

Country of Publication:: United States

Language:: ENGLISH

References (43)

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
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
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
Probing the Energy Landscape of Activation Gating of the Bacterial Potassium Channel KcsA Linder, Tobias; de Groot, Bert L.; Stary-Weinzinger, Anna PLoS Computational Biology, Vol. 9, Issue 5 https://doi.org/10.1371/journal.pcbi.1003058	journal	May 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
A unified formulation of the constant temperature molecular dynamics methods Nosé, Shuichi The Journal of Chemical Physics, Vol. 81, Issue 1 https://doi.org/10.1063/1.447334	journal	July 1984
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
LINCS: A linear constraint solver for molecular simulations Hess, Berk; Bekker, Henk; Berendsen, Herman J. C. Journal of Computational Chemistry, Vol. 18, Issue 12 https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.3.CO;2-L	journal	September 1997
ATP and Sulfonylurea Sensitivity of Mutant ATP-Sensitive K+ Channels in Neonatal Diabetes Koster, Joseph C.; Remedi, Maria S.; Dao, Crystal Diabetes, Vol. 54, Issue 9 https://doi.org/10.2337/diabetes.54.9.2645	journal	September 2005
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
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
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
How proteins adapt to a membrane–water interface Killian, J. Antoinette; von Heijne, Gunnar Trends in Biochemical Sciences, Vol. 25, Issue 9 https://doi.org/10.1016/S0968-0004(00)01626-1	journal	September 2000
Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features Proks, Peter; Antcliff, Jennifer F.; Lippiat, Jon Proceedings of the National Academy of Sciences, Vol. 101, Issue 50 https://doi.org/10.1073/pnas.0404756101	journal	December 2004
Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature Berger, O.; Edholm, O.; Jähnig, F. Biophysical Journal, Vol. 72, Issue 5 https://doi.org/10.1016/S0006-3495(97)78845-3	journal	May 1997
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
The Preference of Tryptophan for Membrane Interfaces ^† Yau, Wai-Ming; Wimley, William C.; Gawrisch, Klaus Biochemistry, Vol. 37, Issue 42 https://doi.org/10.1021/bi980809c	journal	October 1998
Experimentally determined hydrophobicity scale for proteins at membrane interfaces Wimley, William C.; White, Stephen H. Nature Structural & Molecular Biology, Vol. 3, Issue 10 https://doi.org/10.1038/nsb1096-842	journal	October 1996
Engineered interaction between SUR1 and Kir6.2 that enhances ATP sensitivity in KATP channels Pratt, Emily B.; Zhou, Qing; Gay, Joel W. Journal of General Physiology, Vol. 140, Issue 2 https://doi.org/10.1085/jgp.201210803	journal	July 2012
Crystal structure and mechanism of a calcium-gated potassium channel Jiang, Youxing; Lee, Alice; Chen, Jiayun Nature, Vol. 417, Issue 6888 https://doi.org/10.1038/417515a	journal	May 2002
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
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
NMR Analyses of the Gβγ Binding and Conformational Rearrangements of the Cytoplasmic Pore of G Protein-activated Inwardly Rectifying Potassium Channel 1 (GIRK1) Yokogawa, Mariko; Osawa, Masanori; Takeuchi, Koh Journal of Biological Chemistry, Vol. 286, Issue 3 https://doi.org/10.1074/jbc.M110.160754	journal	November 2010
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
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
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
A discrete alcohol pocket involved in GIRK channel activation Aryal, Prafulla; Dvir, Hay; Choe, Senyon Nature Neuroscience, Vol. 12, Issue 8 https://doi.org/10.1038/nn.2358	journal	June 2009
Polymorphic transitions in single crystals: A new molecular dynamics method Parrinello, M.; Rahman, A. Journal of Applied Physics, Vol. 52, Issue 12 https://doi.org/10.1063/1.328693	journal	December 1981
Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing McCusker, Emily C.; Bagnéris, Claire; Naylor, Claire E. Nature Communications, Vol. 3, Issue 1 https://doi.org/10.1038/ncomms2077	journal	January 2012
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels Rohacs, T.; Lopes, C. M. B.; Jin, T. Proceedings of the National Academy of Sciences, Vol. 100, Issue 2 https://doi.org/10.1073/pnas.0236364100	journal	January 2003
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
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
The Aromatic Residues Trp and Phe Have Different Effects on the Positioning of a Transmembrane Helix in the Microsomal Membrane Braun, Paula; von Heijne, Gunnar Biochemistry, Vol. 38, Issue 30 https://doi.org/10.1021/bi990923a	journal	July 1999
Alterations in Conserved Kir Channel-PIP2 Interactions Underlie Channelopathies Lopes, Coeli M. B.; Zhang, Hailin; Rohacs, Tibor Neuron, Vol. 34, Issue 6 https://doi.org/10.1016/S0896-6273(02)00725-0	journal	June 2002
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation Hess, Berk; Kutzner, Carsten; van der Spoel, David Journal of Chemical Theory and Computation, Vol. 4, Issue 3 https://doi.org/10.1021/ct700301q	journal	February 2008
Energetics and Location of Phosphoinositide Binding in Human Kir2.1 Channels D'Avanzo, Nazzareno; Lee, Sun-Joo; Cheng, Wayland W. L. Journal of Biological Chemistry, Vol. 288, Issue 23 https://doi.org/10.1074/jbc.M113.452540	journal	April 2013
Lipid Organization of the Plasma Membrane Ingólfsson, Helgi I.; Melo, Manuel N.; van Eerden, Floris J. Journal of the American Chemical Society, Vol. 136, Issue 41 https://doi.org/10.1021/ja507832e	journal	October 2014
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
Membrane lipids: where they are and how they behave van Meer, Gerrit; Voelker, Dennis R.; Feigenson, Gerald W. Nature Reviews Molecular Cell Biology, Vol. 9, Issue 2 https://doi.org/10.1038/nrm2330	journal	February 2008
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
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
Canonical dynamics: Equilibrium phase-space distributions Hoover, William G. Physical Review A, Vol. 31, Issue 3 https://doi.org/10.1103/PhysRevA.31.1695	journal	March 1985
g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation Wolf, Maarten G.; Hoefling, Martin; Aponte-Santamaría, Camilo Journal of Computational Chemistry, Vol. 31, Issue 11 https://doi.org/10.1002/jcc.21507	journal	March 2010

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