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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20966 | |||||||||
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Title | structure of human KCNQ1-KCNE3-CaM complex | |||||||||
![]() | human KCNQ1-KCNE3-CaM | |||||||||
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![]() | potassium channel / KCNQ1 / CaM / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() negative regulation of membrane repolarization during ventricular 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 ...negative regulation of membrane repolarization during ventricular 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 / negative regulation of potassium ion export across plasma membrane / iodide transport / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / Phase 3 - rapid repolarisation / membrane repolarization during atrial cardiac muscle cell action potential / membrane repolarization during action potential / regulation of atrial cardiac muscle cell membrane repolarization / Phase 2 - plateau phase / intracellular chloride ion homeostasis / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / negative regulation of delayed rectifier potassium channel activity / renal sodium ion absorption / detection of mechanical stimulus involved in sensory perception of sound / potassium ion export across plasma membrane / atrial cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / auditory receptor cell development / regulation of membrane repolarization / protein phosphatase 1 binding / delayed rectifier potassium channel activity / ventricular cardiac muscle cell action potential / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / potassium ion homeostasis / non-motile cilium assembly / regulation of ventricular cardiac muscle cell membrane repolarization / cardiac muscle cell contraction / outward rectifier potassium channel activity / intestinal absorption / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / 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 / inner ear morphogenesis / CREB1 phosphorylation through the activation of Adenylate Cyclase / CaMK IV-mediated phosphorylation of CREB / PKA activation / negative regulation of high voltage-gated calcium channel activity / neuronal cell body membrane / Glycogen breakdown (glycogenolysis) / positive regulation of ryanodine-sensitive calcium-release channel activity / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / sodium ion transport / negative regulation of calcium ion export across plasma membrane / organelle localization by membrane tethering / adrenergic receptor signaling pathway / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / cochlea development / regulation of heart contraction / renal absorption / ciliary base / presynaptic endocytosis / regulation of cardiac muscle cell action potential / negative regulation of ryanodine-sensitive calcium-release channel activity / protein kinase A regulatory subunit binding / Synthesis of IP3 and IP4 in the cytosol / regulation of cell communication by electrical coupling involved in cardiac conduction / protein kinase A catalytic subunit binding / Phase 0 - rapid depolarisation / Negative regulation of NMDA receptor-mediated neuronal transmission / potassium ion import across plasma membrane / Unblocking of NMDA receptors, glutamate binding and activation / RHO GTPases activate PAKs / calcineurin-mediated signaling / social behavior / inner ear development / regulation of heart rate by cardiac conduction / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / regulation of ryanodine-sensitive calcium-release channel activity / action potential / Long-term potentiation / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / protein phosphatase activator activity / voltage-gated potassium channel activity / DARPP-32 events / monoatomic ion channel complex / Smooth Muscle Contraction / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / RHO GTPases activate IQGAPs Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Mackinnon R / Sun J | |||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 93.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.2 KB 17.2 KB | Display Display | ![]() |
Images | ![]() | 176.9 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 550.6 KB | Display | ![]() |
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Full document | ![]() | 550.2 KB | Display | |
Data in XML | ![]() | 6.6 KB | Display | |
Data in CIF | ![]() | 7.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6v00MC ![]() 6uzzC ![]() 6v01C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Annotation | human KCNQ1-KCNE3-CaM | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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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: ![]() |
-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 |
-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: ![]() |
Molecular weight | Theoretical: 40.095168 KDa |
Recombinant expression | Organism: ![]() |
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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 94.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-6v00: |