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Nat Commun
2021 May 14;121:2802. doi: 10.1038/s41467-021-23062-7.
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Electromechanical coupling mechanism for activation and inactivation of an HCN channel.
Dai G
,
Aman TK
,
DiMaio F
,
Zagotta WN
.
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Pacemaker hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels exhibit a reversed voltage-dependent gating, activating by membrane hyperpolarization instead of depolarization. Sea urchin HCN (spHCN) channels also undergo inactivation with hyperpolarization which occurs only in the absence of cyclic nucleotide. Here we applied transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels. We found that removing cAMP produced a largely rigid-body rotation of the C-linker relative to the transmembrane domain, bringing the A' helix of the C-linker in close proximity to the voltage-sensing S4 helix. In addition, rotation of the C-linker was elicited by hyperpolarization in the absence but not the presence of cAMP. These results suggest that - in contrast to electromechanical coupling for channel activation - the A' helix serves to couple the S4-helix movement for channel inactivation, which is likely a conserved mechanism for CNBD-family channels.
Aldrich,
Fifty years of inactivation.
2001, Pubmed
Aldrich,
Fifty years of inactivation.
2001,
Pubmed
Aman,
Regulation of CNGA1 Channel Gating by Interactions with the Membrane.
2016,
Pubmed
,
Xenbase
Baker,
Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.
2015,
Pubmed
Catterall,
The chemical basis for electrical signaling.
2017,
Pubmed
Chatterjee,
A genetically encoded fluorescent probe in mammalian cells.
2013,
Pubmed
Clark,
Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1.
2020,
Pubmed
Cowgill,
Bipolar switching by HCN voltage sensor underlies hyperpolarization activation.
2019,
Pubmed
,
Xenbase
Craven,
Salt bridges and gating in the COOH-terminal region of HCN2 and CNGA1 channels.
2004,
Pubmed
,
Xenbase
Craven,
CNG and HCN channels: two peas, one pod.
2006,
Pubmed
Dai,
The HCN channel voltage sensor undergoes a large downward motion during hyperpolarization.
2019,
Pubmed
Dai,
Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels.
2017,
Pubmed
,
Xenbase
DeBerg,
Structure and Energetics of Allosteric Regulation of HCN2 Ion Channels by Cyclic Nucleotides.
2016,
Pubmed
Decher,
Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated pacemaker channels: molecular coupling between the S4-S5 and C-linkers.
2004,
Pubmed
,
Xenbase
DiFrancesco,
Characterization of single pacemaker channels in cardiac sino-atrial node cells.
,
Pubmed
Evans,
Allosteric conformational change of a cyclic nucleotide-gated ion channel revealed by DEER spectroscopy.
2020,
Pubmed
Flynn,
Insights into the molecular mechanism for hyperpolarization-dependent activation of HCN channels.
2018,
Pubmed
Flynn,
Molecular mechanism underlying phosphatidylinositol 4,5-bisphosphate-induced inhibition of SpIH channels.
2011,
Pubmed
Gauss,
Molecular identification of a hyperpolarization-activated channel in sea urchin sperm.
1998,
Pubmed
Gordon,
Visualizing conformational dynamics of proteins in solution and at the cell membrane.
2018,
Pubmed
Guo,
Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.
2016,
Pubmed
Horrocks,
Energy transfer between terbium (III) and cobalt (II) in thermolysin: a new class of metal--metal distance probes.
1975,
Pubmed
Idikuda,
cAMP binds to closed, inactivated, and open sea urchin HCN channels in a state-dependent manner.
2019,
Pubmed
,
Xenbase
James,
Structural insights into the mechanisms of CNBD channel function.
2018,
Pubmed
James,
CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel.
2017,
Pubmed
Kasimova,
Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.
2019,
Pubmed
Lee,
Voltage Sensor Movements during Hyperpolarization in the HCN Channel.
2019,
Pubmed
Lee,
Structures of the Human HCN1 Hyperpolarization-Activated Channel.
2017,
Pubmed
Li,
Structure of a eukaryotic cyclic-nucleotide-gated channel.
2017,
Pubmed
Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed
Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed
Lu,
Coupling between voltage sensors and activation gate in voltage-gated K+ channels.
2002,
Pubmed
,
Xenbase
Lörinczi,
Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.
2015,
Pubmed
,
Xenbase
Marchesi,
An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel.
2018,
Pubmed
Männikkö,
Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages.
2002,
Pubmed
,
Xenbase
Prole,
Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and Post-S6.
2006,
Pubmed
Ramentol,
Gating mechanism of hyperpolarization-activated HCN pacemaker channels.
2020,
Pubmed
Robertson,
hERG Function in Light of Structure.
2020,
Pubmed
Robinson,
Hyperpolarization-activated cation currents: from molecules to physiological function.
2003,
Pubmed
Rohl,
Protein structure prediction using Rosetta.
2004,
Pubmed
Schmidpeter,
Prolyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel.
2020,
Pubmed
Schneider,
NIH Image to ImageJ: 25 years of image analysis.
2012,
Pubmed
Shin,
Inactivation in HCN channels results from reclosure of the activation gate: desensitization to voltage.
2004,
Pubmed
Song,
High-resolution comparative modeling with RosettaCM.
2013,
Pubmed
Taraska,
Fluorescence applications in molecular neurobiology.
2010,
Pubmed
Taraska,
Mapping the structure and conformational movements of proteins with transition metal ion FRET.
2009,
Pubmed
Tomczak,
A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore.
2017,
Pubmed
,
Xenbase
Vemana,
S4 movement in a mammalian HCN channel.
2004,
Pubmed
,
Xenbase
Wainger,
Molecular mechanism of cAMP modulation of HCN pacemaker channels.
2001,
Pubmed
Wang,
Cryo-EM Structure of the Open Human Ether-à-go-go-Related K+ Channel hERG.
2017,
Pubmed
Whicher,
Regulation of Eag1 gating by its intracellular domains.
2019,
Pubmed
,
Xenbase
Whicher,
Structure of the voltage-gated K⁺ channel Eag1 reveals an alternative voltage sensing mechanism.
2016,
Pubmed
Wisedchaisri,
Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel.
2019,
Pubmed
Xue,
Structural mechanisms of gating and selectivity of human rod CNGA1 channel.
2021,
Pubmed
Zagotta,
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
2003,
Pubmed
Zheng,
Patch-clamp fluorometry recording of conformational rearrangements of ion channels.
2003,
Pubmed
,
Xenbase
Zheng,
Mechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel.
2020,
Pubmed
Zhou,
A conserved tripeptide in CNG and HCN channels regulates ligand gating by controlling C-terminal oligomerization.
2004,
Pubmed
,
Xenbase