XB-ART-50436
Neuron
2014 Dec 17;846:1198-212. doi: 10.1016/j.neuron.2014.11.017.
Show Gene links
Show Anatomy links
Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels.
Lolicato M
,
Riegelhaupt PM
,
Arrigoni C
,
Clark KA
,
Minor DL
.
???displayArticle.abstract???
Mechanical and thermal activation of ion channels is central to touch, thermosensation, and pain. The TRAAK/TREK K(2P) potassium channel subfamily produces background currents that alter neuronal excitability in response to pressure, temperature, signaling lipids, and anesthetics. How such diverse stimuli control channel function is unclear. Here we report structures of K(2P)4.1 (TRAAK) bearing C-type gate-activating mutations that reveal a tilting and straightening of the M4 inner transmembrane helix and a buckling of the M2 transmembrane helix. These conformational changes move M4 in a direction opposite to that in classical potassium channel activation mechanisms and open a passage lateral to the pore that faces the lipid bilayer inner leaflet. Together, our findings uncover a unique aspect of K(2P) modulation, indicate a means for how the K(2P) C-terminal cytoplasmic domain affects the C-type gate which lies ∼40Å away, and suggest how lipids and bilayer inner leaflet deformations may gate the channel.
???displayArticle.pubmedLink??? 25500157
???displayArticle.pmcLink??? PMC4270892
???displayArticle.link??? Neuron
???displayArticle.grants??? [+]
R01 MH093603 NIMH NIH HHS, R01-MH093603 NIMH NIH HHS
Species referenced: Xenopus laevis
Genes referenced: kcnk4
References [+] :
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams, PHENIX: a comprehensive Python-based system for macromolecular structure solution. 2010, Pubmed
Alloui, TREK-1, a K+ channel involved in polymodal pain perception. 2006, Pubmed
Andres-Enguix, Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channel from Lymnaea stagnalis. 2007, Pubmed
Anishkin, Feeling the hidden mechanical forces in lipid bilayer is an original sense. 2014, Pubmed
Bagriantsev, Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains. 2012, Pubmed , Xenbase
Bagriantsev, A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels. 2013, Pubmed
Bagriantsev, Multiple modalities converge on a common gate to control K2P channel function. 2011, Pubmed
Bagriantsev, Piezo proteins: regulators of mechanosensation and other cellular processes. 2014, Pubmed
Baldwin, Temperature dependence of the hydrophobic interaction in protein folding. 1986, Pubmed
Bandell, From chills to chilis: mechanisms for thermosensation and chemesthesis via thermoTRPs. 2007, Pubmed
Bang, TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. 2000, Pubmed
Bavro, Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating. 2012, Pubmed
Brohawn, Domain-swapped chain connectivity and gated membrane access in a Fab-mediated crystal of the human TRAAK K+ channel. 2013, Pubmed
Brohawn, Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel. 2012, Pubmed
Brohawn, Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels. 2014, Pubmed
Cao, TRPV1 structures in distinct conformations reveal activation mechanisms. 2013, Pubmed
Chemin, Lysophosphatidic acid-operated K+ channels. 2005, Pubmed
Chemin, Up- and down-regulation of the mechano-gated K(2P) channel TREK-1 by PIP (2) and other membrane phospholipids. 2007, Pubmed
Chemin, A phospholipid sensor controls mechanogating of the K+ channel TREK-1. 2005, Pubmed
Chowdhury, A molecular framework for temperature-dependent gating of ion channels. 2014, Pubmed
Clapham, A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. 2011, Pubmed
Clarke, The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. 2008, Pubmed
Cohen, A novel mechanism for human K2P2.1 channel gating. Facilitation of C-type gating by protonation of extracellular histidine residues. 2008, Pubmed , Xenbase
Collaborative Computational Project, Number 4, The CCP4 suite: programs for protein crystallography. 1994, Pubmed
Conway, Covalent modification of a volatile anesthetic regulatory site activates TASK-3 (KCNK9) tandem-pore potassium channels. 2012, Pubmed
Cordes, Proline-induced distortions of transmembrane helices. 2002, Pubmed
Cuello, Structural mechanism of C-type inactivation in K(+) channels. 2010, Pubmed
Cuello, Structural basis for the coupling between activation and inactivation gates in K(+) channels. 2010, Pubmed
Dedman, The mechano-gated K(2P) channel TREK-1. 2009, Pubmed
Diederichs, Better models by discarding data? 2013, Pubmed
Doyle, The structure of the potassium channel: molecular basis of K+ conduction and selectivity. 1998, Pubmed
Drew, GFP-based optimization scheme for the overexpression and purification of eukaryotic membrane proteins in Saccharomyces cerevisiae. 2008, Pubmed
Emsley, Coot: model-building tools for molecular graphics. 2004, Pubmed
Enyedi, Molecular background of leak K+ currents: two-pore domain potassium channels. 2010, Pubmed
Evans, How good are my data and what is the resolution? 2013, Pubmed
Faham, Side-chain contributions to membrane protein structure and stability. 2004, Pubmed
Fink, Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. 1996, Pubmed , Xenbase
Fink, A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. 1998, Pubmed , Xenbase
Foadi, Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography. 2013, Pubmed
Haswell, Mechanosensitive channels: what can they do and how do they do it? 2011, Pubmed
Honoré, The neuronal background K2P channels: focus on TREK1. 2007, Pubmed
Honoré, An intracellular proton sensor commands lipid- and mechano-gating of the K(+) channel TREK-1. 2002, Pubmed
Jiang, The open pore conformation of potassium channels. 2002, Pubmed
Jordt, Lessons from peppers and peppermint: the molecular logic of thermosensation. 2003, Pubmed
Julius, TRP channels and pain. 2013, Pubmed
Kabsch, XDS. 2010, Pubmed
Kamajaya, The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold. 2014, Pubmed
Kang, Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. 2005, Pubmed
Karplus, Linking crystallographic model and data quality. 2012, Pubmed
Kawate, Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins. 2006, Pubmed
Kim, Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali. 2001, Pubmed
Kim, Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi. 2001, Pubmed
Kung, Mechanosensitive channels in microbes. 2010, Pubmed
Kung, A possible unifying principle for mechanosensation. 2005, Pubmed
Lesage, Molecular physiology of pH-sensitive background K(2P) channels. 2011, Pubmed
Lesage, Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. 2000, Pubmed
Lesage, Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel. 2000, Pubmed
Liao, Structure of the TRPV1 ion channel determined by electron cryo-microscopy. 2013, Pubmed
Lopes, PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels. 2005, Pubmed , Xenbase
Lopes, Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. 2000, Pubmed , Xenbase
Magidovich, Conserved gating hinge in ligand- and voltage-dependent K+ channels. 2004, Pubmed , Xenbase
Maingret, Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. 1999, Pubmed
Maingret, Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. 2000, Pubmed
Maingret, TRAAK is a mammalian neuronal mechano-gated K+ channel. 1999, Pubmed
Maingret, TREK-1 is a heat-activated background K(+) channel. 2000, Pubmed , Xenbase
Mathie, Gating of two pore domain potassium channels. 2010, Pubmed
McCusker, Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing. 2012, Pubmed
Miller, Crystal structure of the human two-pore domain potassium channel K2P1. 2012, Pubmed
Murbartián, Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. 2005, Pubmed
Newstead, High-throughput fluorescent-based optimization of eukaryotic membrane protein overexpression and purification in Saccharomyces cerevisiae. 2007, Pubmed
Niemeyer, Separate gating mechanisms mediate the regulation of K2P potassium channel TASK-2 by intra- and extracellular pH. 2010, Pubmed
Nilius, Sensing pressure with ion channels. 2012, Pubmed
Noël, The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. 2009, Pubmed
Noël, Molecular regulations governing TREK and TRAAK channel functions. 2011, Pubmed
Patel, Inhalational anesthetics activate two-pore-domain background K+ channels. 1999, Pubmed
Patel, A mammalian two pore domain mechano-gated S-like K+ channel. 1998, Pubmed
Payandeh, The crystal structure of a voltage-gated sodium channel. 2011, Pubmed
Payandeh, Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. 2012, Pubmed
Payandeh, Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. 2015, Pubmed
Pereira, Role of the TREK2 potassium channel in cold and warm thermosensation and in pain perception. 2014, Pubmed
Piechotta, The pore structure and gating mechanism of K2P channels. 2011, Pubmed
Privalov, Stability of protein structure and hydrophobic interaction. 1988, Pubmed
Rapedius, State-independent intracellular access of quaternary ammonium blockers to the pore of TREK-1. 2012, Pubmed , Xenbase
Sandoz, Optical probing of a dynamic membrane interaction that regulates the TREK1 channel. 2011, Pubmed , Xenbase
Sandoz, Mtap2 is a constituent of the protein network that regulates twik-related K+ channel expression and trafficking. 2008, Pubmed , Xenbase
Segal-Hayoun, Molecular mechanisms underlying membrane-potential-mediated regulation of neuronal K2P2.1 channels. 2010, Pubmed , Xenbase
Shaya, Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels. 2014, Pubmed
Shaya, Voltage-gated sodium channel (NaV) protein dissection creates a set of functional pore-only proteins. 2011, Pubmed
Talley, Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action. 2002, Pubmed
Tsunozaki, Mammalian somatosensory mechanotransduction. 2009, Pubmed
Uysal, Crystal structure of full-length KcsA in its closed conformation. 2009, Pubmed
Vay, The thermo-TRP ion channel family: properties and therapeutic implications. 2012, Pubmed
Vriens, Peripheral thermosensation in mammals. 2014, Pubmed
Whorton, Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium. 2011, Pubmed , Xenbase
Yohannan, The evolution of transmembrane helix kinks and the structural diversity of G protein-coupled receptors. 2004, Pubmed
Yohannan, Proline substitutions are not easily accommodated in a membrane protein. 2004, Pubmed
Zhang, Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. 2012, Pubmed