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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Ion channel | |||||||||
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![]() | ion channel / TRANSPORT PROTEIN | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.83 Å | |||||||||
![]() | Jiang D / Zhang J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: N-type fast inactivation of a eukaryotic voltage-gated sodium channel. Authors: Jiangtao Zhang / Yiqiang Shi / Junping Fan / Huiwen Chen / Zhanyi Xia / Bo Huang / Juquan Jiang / Jianke Gong / Zhuo Huang / Daohua Jiang / ![]() Abstract: Voltage-gated sodium (Na) channels initiate action potentials. Fast inactivation of Na channels, mediated by an Ile-Phe-Met motif, is crucial for preventing hyperexcitability and regulating firing ...Voltage-gated sodium (Na) channels initiate action potentials. Fast inactivation of Na channels, mediated by an Ile-Phe-Met motif, is crucial for preventing hyperexcitability and regulating firing frequency. Here we present cryo-electron microscopy structure of NaEh from the coccolithophore Emiliania huxleyi, which reveals an unexpected molecular gating mechanism for Na channel fast inactivation independent of the Ile-Phe-Met motif. An N-terminal helix of NaEh plugs into the open activation gate and blocks it. The binding pose of the helix is stabilized by multiple electrostatic interactions. Deletion of the helix or mutations blocking the electrostatic interactions completely abolished the fast inactivation. These strong interactions enable rapid inactivation, but also delay recovery from fast inactivation, which is ~160-fold slower than human Na channels. Together, our results provide mechanistic insights into fast inactivation of NaEh that fundamentally differs from the conventional local allosteric inhibition, revealing both surprising structural diversity and functional conservation of ion channel inactivation. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.4 KB 10.4 KB | Display Display | ![]() |
Images | ![]() | 151.9 KB | ||
Filedesc metadata | ![]() | 5.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 500.3 KB | Display | ![]() |
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Full document | ![]() | 499.9 KB | Display | |
Data in XML | ![]() | 6.3 KB | Display | |
Data in CIF | ![]() | 7.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : ion channel complex
Entire | Name: ion channel complex |
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Components |
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-Supramolecule #1: ion channel complex
Supramolecule | Name: ion channel complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: ion channel,GFP-TwinStrep
Macromolecule | Name: ion channel,GFP-TwinStrep / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 91.684469 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MIAAIHNARR KKREAAAAHK AQHRTAENSM DSLEDSTHET DAGERAQAGS TKLAWTDVVA PPPRKVVFWL PHQRKVFDFY ASQGVQYFT AFLIVSNFIF NCAEKEWDPY TDQLYQGLWR WGEFAFNTMF LIELLINFYG IAFCFWRYNW AWNTFDLVVV A IGTLTMAE ...String: MIAAIHNARR KKREAAAAHK AQHRTAENSM DSLEDSTHET DAGERAQAGS TKLAWTDVVA PPPRKVVFWL PHQRKVFDFY ASQGVQYFT AFLIVSNFIF NCAEKEWDPY TDQLYQGLWR WGEFAFNTMF LIELLINFYG IAFCFWRYNW AWNTFDLVVV A IGTLTMAE AIGGNFMPPS MALIRNLRAF RIFRLFKRIK SLNKIIVSLG KAIPGVANAF VIMVIIMCIY AILGVEFYHM TG SDGTYVT YNDNVKRGLC TGDEVELGQC SLNQTVSSET ARGYTYGEEY YGTFFRALYT LFQVLTGESW SEAVARPAVF ESH YDSFGP VLFYVSFIII CQIVLINVVV AVLLDKMVEE DDSEDPEKQT VAEKLSEMLS QEHAQLREIF RTWDEDNSGT ISIK EWRKA VKSMGYRGPI DVLDQIFASM DKDHSGELDY AEIDRMLSPT AARERRSSTH ANPKRSVKEE VVAMRAEFTD HVARL ETQI AALVLELQLQ RKPCGAEAPA PAHSRLAHDS DGAPTEPPPP AAPDHHHLED DEDTTQRVAA ALEVLFQGPS KGEELF TGV VPILVELDGD VNGHKFSVRG EGEGDATNGK LTLKFICTTG KLPVPWPTLV TTLTYGVQCF SRYPDHMKRH DFFKSAM PE GYVQERTISF KDDGTYKTRA EVKFEGDTLV NRIELKGIDF KEDGNILGHK LEYNFNSHNV YITADKQKNG IKANFKIR H NVEDGSVQLA DHYQQNTPIG DGPVLLPDNH YLSTQSVLSK DPNEKRDHMV LLEFVTAAGI THGMDEWSHP QFEKGGGSG GGSGGSAWSH PQFEK |
-Macromolecule #2: ion channel
Macromolecule | Name: ion channel / type: protein_or_peptide / ID: 2 / Details: N-terminal helix of either of the four protomers / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 1.913298 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MIAAIHNARR KKREAAA |
-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: 7.5 |
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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: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.83 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 61065 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |