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Open data
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Basic information
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Title | KCNQ1 with voltage sensor in the down conformation | |||||||||
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![]() | voltage-gated potassium channel / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / lumenal side of membrane / negative regulation of voltage-gated potassium channel activity / rhythmic behavior / regulation of gastric acid secretion / stomach development / membrane repolarization during atrial cardiac muscle cell action potential ...gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / lumenal side of membrane / negative regulation of voltage-gated potassium channel activity / rhythmic behavior / regulation of gastric acid secretion / stomach development / membrane repolarization during atrial cardiac muscle cell action potential / Phase 3 - rapid repolarisation / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during action potential / iodide transport / membrane repolarization during ventricular cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / Phase 2 - plateau phase / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane / intracellular chloride ion homeostasis / renal sodium ion absorption / negative regulation of delayed rectifier potassium channel activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / atrial cardiac muscle cell action potential / detection of mechanical stimulus involved in sensory perception of sound / auditory receptor cell development / regulation of membrane repolarization / protein phosphatase 1 binding / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / potassium ion homeostasis / ventricular cardiac muscle cell action potential / non-motile cilium assembly / delayed rectifier potassium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / outward rectifier potassium channel activity / CaM pathway / intestinal absorption / Cam-PDE 1 activation / Sodium/Calcium exchangers / Calmodulin induced events / Reduction of cytosolic Ca++ levels / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / monoatomic ion channel complex / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / ciliary base / CaMK IV-mediated phosphorylation of CREB / positive regulation of cyclic-nucleotide phosphodiesterase activity / Glycogen breakdown (glycogenolysis) / regulation of heart contraction / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / inner ear morphogenesis / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / positive regulation of heart rate / Activation of RAC1 downstream of NMDARs / renal absorption / cochlea development / adrenergic receptor signaling pathway / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / voltage-gated potassium channel activity / Phase 0 - rapid depolarisation / protein kinase A regulatory subunit binding / protein phosphatase activator activity / regulation of heart rate by cardiac conduction / potassium ion import across plasma membrane / protein kinase A catalytic subunit binding / RHO GTPases activate PAKs / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / social behavior / inner ear development / Long-term potentiation / Uptake and function of anthrax toxins / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / detection of calcium ion / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / calcium channel inhibitor activity / RHO GTPases activate IQGAPs / cellular response to interferon-beta / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / eNOS activation Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.8 Å | |||||||||
![]() | Mandala VS / MacKinnon R | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The membrane electric field regulates the PIP-binding site to gate the KCNQ1 channel. Authors: Venkata Shiva Mandala / Roderick MacKinnon / ![]() Abstract: Voltage-dependent ion channels underlie the propagation of action potentials and other forms of electrical activity in cells. In these proteins, voltage sensor domains (VSDs) regulate opening and ...Voltage-dependent ion channels underlie the propagation of action potentials and other forms of electrical activity in cells. In these proteins, voltage sensor domains (VSDs) regulate opening and closing of the pore through the displacement of their positive-charged S4 helix in response to the membrane voltage. The movement of S4 at hyperpolarizing membrane voltages in some channels is thought to directly clamp the pore shut through the S4-S5 linker helix. The KCNQ1 channel (also known as K7.1), which is important for heart rhythm, is regulated not only by membrane voltage but also by the signaling lipid phosphatidylinositol 4,5-bisphosphate (PIP). KCNQ1 requires PIP to open and to couple the movement of S4 in the VSD to the pore. To understand the mechanism of this voltage regulation, we use cryogenic electron microscopy to visualize the movement of S4 in the human KCNQ1 channel in lipid membrane vesicles with a voltage difference across the membrane, i.e., an applied electric field in the membrane. Hyperpolarizing voltages displace S4 in such a manner as to sterically occlude the PIP-binding site. Thus, in KCNQ1, the voltage sensor acts primarily as a regulator of PIP binding. The voltage sensors' influence on the channel's gate is indirect through the reaction sequence: voltage sensor movement → alter PIP ligand affinity → alter pore opening. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 19.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.8 KB 16.8 KB | Display Display | ![]() |
Images | ![]() | 80 KB | ||
Filedesc metadata | ![]() | 5.5 KB | ||
Others | ![]() ![]() ![]() | 15.6 MB 15.8 MB 15.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 869 KB | Display | ![]() |
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Full document | ![]() | 868.6 KB | Display | |
Data in XML | ![]() | 9.7 KB | Display | |
Data in CIF | ![]() | 11.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8sinMC ![]() 8sikC ![]() 8simC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.678 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
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Density Histograms |
-Half map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
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Sample components
-Entire : Complex of KCNQ1 (Kv7.1) channel bound to calmodulin-Ca2+
Entire | Name: Complex of KCNQ1 (Kv7.1) channel bound to calmodulin-Ca2+ |
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Components |
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-Supramolecule #1: Complex of KCNQ1 (Kv7.1) channel bound to calmodulin-Ca2+
Supramolecule | Name: Complex of KCNQ1 (Kv7.1) channel bound to calmodulin-Ca2+ type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Potassium voltage-gated channel subfamily KQT member 1
Macromolecule | Name: Potassium voltage-gated channel subfamily KQT member 1 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 63.258574 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASDLGPRPP VSLDPRVSIY STRRPVLART HVQGRVYNFL ERPTGWKCFV YHFAVFLIVL VCLIFSVLST IEQYAALATG TLFWMEIVL VVFFGTEYVV RLWSAGCRSK YVGLWGRLRF ARKPISIIDL IVVVASMVVL CVGSKGQVFA TSAIRGIRFL Q ILRMLHVD ...String: MASDLGPRPP VSLDPRVSIY STRRPVLART HVQGRVYNFL ERPTGWKCFV YHFAVFLIVL VCLIFSVLST IEQYAALATG TLFWMEIVL VVFFGTEYVV RLWSAGCRSK YVGLWGRLRF ARKPISIIDL IVVVASMVVL CVGSKGQVFA TSAIRGIRFL Q ILRMLHVD RQGGTWRLLG SVVFIHRQEL ITTLYIGFLG LIFSSYFVYL AEKDAVNESG RVEFGSYADA LWWGVVTVTT IG YGDKVPQ TWVGKTIASC FSVFAISFFA LPAGILGSGF ALKVQQKQRQ KHFNRQIPAA ASLIQTAWRC YAAENPDSST WKI YIRKAP RSHTLLSPSP KPKKSVVVKK KKFKLDKDNG VTPGEKMLTV PHITCDPPEE RRLDHFSVDG YDSSVRKSPT LLEV SMPHF MRTNSFAEDL DLEGETLLTP ITHISQLREH HRATIKVIRR MQYFVAKKKF QQARKPYDVR DVIEQYSQGH LNLMV RIKE LQRRLDQSIG KPSLFISVSE KSKDRGSNTI GARLNRVEDK VTQLDQRLAL ITDMLHQLLS LHSNSLEVLF QGP UniProtKB: Potassium voltage-gated channel subfamily KQT member 1 |
-Macromolecule #2: Calmodulin-1
Macromolecule | Name: Calmodulin-1 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 16.852545 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK UniProtKB: Calmodulin-1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 6.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 34096 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |