+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20967 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | structure of human KCNQ1-KCNE3-CaM complex with PIP2 | |||||||||
Map data | KCNQ1-KCNE3-CaM complex with PIP2 | |||||||||
Sample |
| |||||||||
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 / 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 / sodium ion transport / adrenergic receptor signaling pathway / renal absorption / positive regulation of ryanodine-sensitive calcium-release channel activity / neuronal cell body membrane / 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 / bioluminescence / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Mackinnon R / Sun J | |||||||||
Funding support | United States, 2 items
| |||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20967.map.gz | 7.9 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-20967-v30.xml emd-20967.xml | 12.5 KB 12.5 KB | Display Display | EMDB header |
Images | emd_20967.png | 152 KB | ||
Filedesc metadata | emd-20967.cif.gz | 5.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20967 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20967 | HTTPS FTP |
-Validation report
Summary document | emd_20967_validation.pdf.gz | 373.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_20967_full_validation.pdf.gz | 373.5 KB | Display | |
Data in XML | emd_20967_validation.xml.gz | 6.2 KB | Display | |
Data in CIF | emd_20967_validation.cif.gz | 7.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20967 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20967 | HTTPS FTP |
-Related structure data
Related structure data | 6v01MC 6uzzC 6v00C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_20967.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | KCNQ1-KCNE3-CaM complex with PIP2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.09 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : KCNQ1-CaM complex
Entire | Name: KCNQ1-CaM complex |
---|---|
Components |
|
-Supramolecule #1: KCNQ1-CaM complex
Supramolecule | Name: KCNQ1-CaM complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
---|---|
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 |
---|---|
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 E member 3
Macromolecule | Name: Potassium voltage-gated channel subfamily E member 3 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.725399 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: METTNGTETW YESLHAVLKA LNATLHSNLL CRPGPGLGPD NQTEERRASL PGRDDNSYMY ILFVMFLFAV TVGSLILGYT RSRKVDKRS DPYHVYIKNR VSMI UniProtKB: Potassium voltage-gated channel subfamily E member 3 |
-Macromolecule #3: Potassium voltage-gated channel subfamily KQT member 1
Macromolecule | Name: Potassium voltage-gated channel subfamily KQT member 1 type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
---|---|
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 #4: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 4 / Number of copies: 8 / Formula: CA |
---|---|
Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #5: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...
Macromolecule | Name: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate type: ligand / ID: 5 / Number of copies: 4 / Formula: PT5 |
---|---|
Molecular weight | Theoretical: 1.047088 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 73640 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
---|---|
Output model | PDB-6v01: |