+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33316 | |||||||||||||||||||||
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Title | human KCNQ1-CaM in apo state | |||||||||||||||||||||
Map data | ||||||||||||||||||||||
Sample |
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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 / membrane repolarization during action potential / membrane repolarization during ventricular cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / iodide transport / Phase 2 - plateau phase / potassium ion export across plasma membrane / membrane repolarization during cardiac muscle cell action potential / 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 / 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 / Voltage gated Potassium channels / outward rectifier potassium channel activity / potassium ion homeostasis / ventricular cardiac muscle cell action potential / non-motile cilium assembly / regulation of ventricular cardiac muscle cell membrane repolarization / intestinal absorption / regulation of heart contraction / negative regulation of high voltage-gated calcium channel activity / monoatomic ion channel complex / ciliary base / inner ear morphogenesis / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of heart rate / cochlea development / renal absorption / adrenergic receptor signaling pathway / potassium ion import across plasma membrane / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / protein kinase A regulatory subunit binding / regulation of heart rate by cardiac conduction / protein phosphatase activator activity / voltage-gated potassium channel activity / protein kinase A catalytic subunit binding / inner ear development / social behavior / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of phosphoprotein phosphatase activity / adenylate cyclase binding / catalytic complex / detection of calcium ion / negative regulation of ryanodine-sensitive calcium-release channel activity / regulation of cardiac muscle contraction / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / voltage-gated potassium channel complex / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cellular response to cAMP / regulation of calcium-mediated signaling / positive regulation of protein dephosphorylation / titin binding / transport vesicle / positive regulation of protein autophosphorylation / positive regulation of cardiac muscle contraction / potassium ion transmembrane transport / cardiac muscle contraction / sperm midpiece / cellular response to epinephrine stimulus / calcium channel complex / phosphatidylinositol-4,5-bisphosphate binding / substantia nigra development / adenylate cyclase activator activity / regulation of heart rate / protein serine/threonine kinase activator activity / sarcomere / erythrocyte differentiation / positive regulation of peptidyl-threonine phosphorylation / regulation of cytokinesis / spindle microtubule / sensory perception of sound / response to insulin / cytoplasmic vesicle membrane / positive regulation of protein serine/threonine kinase activity / regulation of blood pressure / spindle pole / response to calcium ion / calcium-dependent protein binding / glucose metabolic process Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||||||||
Authors | Ma D / Guo J | |||||||||||||||||||||
Funding support | China, 6 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers. Authors: Demin Ma / Ling Zhong / Zhenzhen Yan / Jing Yao / Yan Zhang / Fan Ye / Yuan Huang / Dongwu Lai / Wei Yang / Panpan Hou / Jiangtao Guo / Abstract: The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 ...The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown. In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP) and a small-molecule ML277, we determined 2.5-3.5 Å resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP-bound open states. ML277 binds at the "elbow" pocket above the S4-S5 linker and directly induces an upward movement of the S4-S5 linker and the opening of the activation gate without affecting the C-terminal domain (CTD) of KCNQ1. PIP binds at the cleft between the VSD and the PD and brings a large structural rearrangement of the CTD together with the CaM to activate the PD. These findings not only elucidate the structural basis for the dynamic VSD-PD coupling process during KCNQ1 gating but also pave the way to develop new therapeutics for anti-arrhythmia. | |||||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33316.map.gz | 43.8 MB | EMDB map data format | |
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Header (meta data) | emd-33316-v30.xml emd-33316.xml | 16.1 KB 16.1 KB | Display Display | EMDB header |
Images | emd_33316.png | 61.9 KB | ||
Others | emd_33316_half_map_1.map.gz emd_33316_half_map_2.map.gz | 37 MB 37 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33316 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33316 | HTTPS FTP |
-Related structure data
Related structure data | 7xniMC 7xnkC 7xnlC 7xnnC 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_33316.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33316_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33316_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-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: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 76.487297 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAAASSPPRA ERKRWGWGRL PGARRGSAGL AKKCPFSLEL AEGGPAGGAL YAPIAPGAPG PAPPASPAAP AAPPVASDLG PRPPVSLDP RVSIYSTRRP VLARTHVQGR VYNFLERPTG WKCFVYHFAV FLIVLVCLIF SVLSTIEQYA ALATGTLFWM E IVLVVFFG ...String: MAAASSPPRA ERKRWGWGRL PGARRGSAGL AKKCPFSLEL AEGGPAGGAL YAPIAPGAPG PAPPASPAAP AAPPVASDLG PRPPVSLDP RVSIYSTRRP VLARTHVQGR VYNFLERPTG WKCFVYHFAV FLIVLVCLIF SVLSTIEQYA ALATGTLFWM E IVLVVFFG TEYVVRLWSA GCRSKYVGLW GRLRFARKPI SIIDLIVVVA SMVVLCVGSK GQVFATSAIR GIRFLQILRM LH VDRQGGT WRLLGSVVFI HRQELITTLY IGFLGLIFSS YFVYLAEKDA VNESGRVEFG SYADALWWGV VTVTTIGYGD KVP QTWVGK TIASCFSVFA ISFFALPAGI LGSGFALKVQ QKQRQKHFNR QIPAAASLIQ TAWRCYAAEN PDSSTWKIYI RKAP RSHTL LSPSPKPKKS VVVKKKKFKL DKDNGVTPGE KMLTVPHITC DPPEERRLDH FSVDGYDSSV RKSPTLLEVS MPHFM RTNS FAEDLDLEGE TLLTPITHIS QLREHHRATI KVIRRMQYFV AKKKFQQARK PYDVRDVIEQ YSQGHLNLMV RIKELQ RRL DQSIGKPSLF ISVSEKSKDR GSNTIGARLN RVEDKVTQLD QRLALITDML HQLLSLHGGS TPGSGGPPRE GGAHITQ PC GSGGSVDPEL FLPSNTLPTY EQLTVPRRGP DEGSLEGGSS GGWSHPQFEK |
-Macromolecule #2: Calmodulin-3
Macromolecule | Name: Calmodulin-3 / 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: 19.615445 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK LEGGSSGGLV P RGSGGSSG GHHHHHHHH |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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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 / Nominal defocus max: -1.3 µm / Nominal defocus min: -1.1 µm |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 64.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 169344 |