+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20966 | |||||||||
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Title | structure of human KCNQ1-KCNE3-CaM complex | |||||||||
Map data | human KCNQ1-KCNE3-CaM | |||||||||
Sample |
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Keywords | potassium channel / KCNQ1 / CaM / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential / negative regulation of potassium ion export across plasma membrane / 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 ...negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential / negative regulation of potassium ion export across plasma membrane / 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 / membrane repolarization during ventricular cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / Phase 2 - plateau phase / iodide transport / potassium ion export across plasma membrane / membrane repolarization during cardiac muscle cell action potential / renal sodium ion absorption / intracellular chloride ion homeostasis / 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 / auditory receptor cell development / detection of mechanical stimulus involved in sensory perception of sound / regulation of membrane repolarization / delayed rectifier potassium channel activity / protein phosphatase 1 binding / positive regulation of potassium ion transmembrane transport / outward rectifier potassium channel activity / Voltage gated Potassium channels / potassium ion homeostasis / ventricular cardiac muscle cell action potential / non-motile cilium assembly / regulation of ventricular cardiac muscle cell membrane repolarization / CaM pathway / Cam-PDE 1 activation / regulation of heart contraction / Sodium/Calcium exchangers / intestinal absorption / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / PKA activation / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of high voltage-gated calcium channel activity / monoatomic ion channel complex / CaMK IV-mediated phosphorylation of CREB / ciliary base / Glycogen breakdown (glycogenolysis) / inner ear morphogenesis / neuronal cell body membrane / negative regulation of calcium ion export across plasma membrane / organelle localization by membrane tethering / positive regulation of heart rate / Activation of RAC1 downstream of NMDARs / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / CLEC7A (Dectin-1) induces NFAT activation / autophagosome membrane docking / sodium ion transport / cochlea development / renal absorption / adrenergic receptor signaling pathway / potassium ion import across plasma membrane / Negative regulation of NMDA receptor-mediated neuronal transmission / positive regulation of ryanodine-sensitive calcium-release channel activity / Unblocking of NMDA receptors, glutamate binding and activation / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / regulation of heart rate by cardiac conduction / Phase 0 - rapid depolarisation / protein phosphatase activator activity / RHO GTPases activate PAKs / protein kinase A regulatory subunit binding / voltage-gated potassium channel activity / protein kinase A catalytic subunit binding / inner ear development / social behavior / positive regulation of cyclic-nucleotide phosphodiesterase activity / Long-term potentiation / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / detection of calcium ion / DARPP-32 events / Smooth Muscle Contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / RHO GTPases activate IQGAPs / potassium channel regulator activity / cellular response to interferon-beta Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Mackinnon R / Sun J | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell / Year: 2020 Title: Structural Basis of Human KCNQ1 Modulation and Gating. Authors: Ji Sun / Roderick MacKinnon / Abstract: KCNQ1, also known as Kv7.1, is a voltage-dependent K channel that regulates gastric acid secretion, salt and glucose homeostasis, and heart rhythm. Its functional properties are regulated in a tissue- ...KCNQ1, also known as Kv7.1, is a voltage-dependent K channel that regulates gastric acid secretion, salt and glucose homeostasis, and heart rhythm. Its functional properties are regulated in a tissue-specific manner through co-assembly with beta subunits KCNE1-5. In non-excitable cells, KCNQ1 forms a complex with KCNE3, which suppresses channel closure at negative membrane voltages that otherwise would close it. Pore opening is regulated by the signaling lipid PIP2. Using cryoelectron microscopy (cryo-EM), we show that KCNE3 tucks its single-membrane-spanning helix against KCNQ1, at a location that appears to lock the voltage sensor in its depolarized conformation. Without PIP2, the pore remains closed. Upon addition, PIP2 occupies a site on KCNQ1 within the inner membrane leaflet, which triggers a large conformational change that leads to dilation of the pore's gate. It is likely that this mechanism of PIP2 activation is conserved among Kv7 channels. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20966.map.gz | 93.9 MB | EMDB map data format | |
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Header (meta data) | emd-20966-v30.xml emd-20966.xml | 12.3 KB 12.3 KB | Display Display | EMDB header |
Images | emd_20966.png | 176.9 KB | ||
Filedesc metadata | emd-20966.cif.gz | 5.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20966 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20966 | HTTPS FTP |
-Related structure data
Related structure data | 6v00MC 6uzzC 6v01C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20966.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | human KCNQ1-KCNE3-CaM | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : KCNQ1-CaM complex
Entire | Name: KCNQ1-CaM complex |
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Components |
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-Supramolecule #1: KCNQ1-CaM complex
Supramolecule | Name: KCNQ1-CaM complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-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: 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 #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: 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 #3: MCherry fluorescent protein,Potassium voltage-gated channel subfa...
Macromolecule | Name: MCherry fluorescent protein,Potassium voltage-gated channel subfamily E member 3 type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.095168 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GGMVSKGEED NMAIIKEFMR FKVHMEGSVN GHEFEIEGEG EGRPYEGTQT AKLKVTKGGP LPFAWDILSP QFMYGSKAYV KHPADIPDY LKLSFPEGFN WERVMNFEDG GVVTVTQDSS LQDGEFIYKV KLRGTNFPSD GPVMQCRTMG WEASTERMYP E DGALKGEI ...String: GGMVSKGEED NMAIIKEFMR FKVHMEGSVN GHEFEIEGEG EGRPYEGTQT AKLKVTKGGP LPFAWDILSP QFMYGSKAYV KHPADIPDY LKLSFPEGFN WERVMNFEDG GVVTVTQDSS LQDGEFIYKV KLRGTNFPSD GPVMQCRTMG WEASTERMYP E DGALKGEI KQRLKLKDGG HYDAEVKTTY KAKKPVQLPG AYNVDIKLDI LSHNEDYTIV EQYERAEGRH STGGMDELYK GS GENLYFQ SSRATMETTN GTETWYESLH AVLKALNATL HSNLLCRPGP GLGPDNQTEE RRASLPGRDD NSYMYILFVM FLF AVTVGS LILGYTRSRK VDKRSDPYHV YIKNRVSMI UniProtKB: MCherry fluorescent protein, Potassium voltage-gated channel subfamily E member 3 |
-Macromolecule #4: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 4 / 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
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 94.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 39074 |
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | PDB-6v00: |