+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40509 | |||||||||
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Title | KCNQ1 with voltage sensor in the intermediate conformation | |||||||||
Map data | ||||||||||
Sample |
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Keywords | voltage-gated potassium channel / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information 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 / iodide transport / membrane repolarization during action potential / 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 / intracellular chloride ion homeostasis / renal sodium ion absorption / negative regulation of delayed rectifier potassium channel activity / potassium ion export across plasma membrane / 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 / outward rectifier potassium channel activity / non-motile cilium assembly / delayed rectifier potassium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / cardiac muscle cell contraction / CaM pathway / Cam-PDE 1 activation / intestinal absorption / 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 / Glycogen breakdown (glycogenolysis) / inner ear morphogenesis / positive regulation of cyclic-nucleotide phosphodiesterase activity / regulation of heart contraction / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / regulation of cardiac muscle cell action potential / Activation of RAC1 downstream of NMDARs / positive regulation of heart rate / cochlea development / adrenergic receptor signaling pathway / renal absorption / 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 / Phase 0 - rapid depolarisation / protein kinase A regulatory subunit binding / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / regulation of heart rate by cardiac conduction / voltage-gated potassium channel activity / potassium ion import across plasma membrane / action potential / protein kinase A catalytic subunit binding / RHO GTPases activate PAKs / : / Ion transport by P-type ATPases / inner ear development / Long-term potentiation / Uptake and function of anthrax toxins / social behavior / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / detection of calcium ion / regulation of cardiac muscle contraction / regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.2 Å | |||||||||
Authors | Mandala VS / MacKinnon R | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 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 | emd_40509.map.gz | 18.8 MB | EMDB map data format | |
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Header (meta data) | emd-40509-v30.xml emd-40509.xml | 17.1 KB 17.1 KB | Display Display | EMDB header |
Images | emd_40509.png | 78.2 KB | ||
Filedesc metadata | emd-40509.cif.gz | 5.6 KB | ||
Others | emd_40509_additional_1.map.gz emd_40509_half_map_1.map.gz emd_40509_half_map_2.map.gz | 13.1 MB 13.2 MB 13.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40509 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40509 | HTTPS FTP |
-Validation report
Summary document | emd_40509_validation.pdf.gz | 800.2 KB | Display | EMDB validaton report |
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Full document | emd_40509_full_validation.pdf.gz | 799.8 KB | Display | |
Data in XML | emd_40509_validation.xml.gz | 9.7 KB | Display | |
Data in CIF | emd_40509_validation.cif.gz | 11.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40509 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40509 | HTTPS FTP |
-Related structure data
Related structure data | 8simMC 8sikC 8sinC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_40509.map.gz / Format: CCP4 / Size: 20.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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
File | emd_40509_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_40509_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_40509_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-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: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Calmodulin-1
Macromolecule | Name: Calmodulin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 16.852545 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK UniProtKB: Calmodulin-1 |
-Macromolecule #2: Potassium voltage-gated channel subfamily KQT member 1
Macromolecule | Name: Potassium voltage-gated channel subfamily KQT member 1 type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 63.258574 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 #3: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 8 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-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: FIELD EMISSION GUN |
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 |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Applied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 24748 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |