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Yorodumi- EMDB-21591: Cryo-EM structure of human Pannexin 1 channel with deletion of N-... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21591 | ||||||||||||
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Title | Cryo-EM structure of human Pannexin 1 channel with deletion of N-terminal helix and C-terminal tail | ||||||||||||
Map data | Unsharpened map of %u0394NTH/%u0394CTT-hsPANX1 | ||||||||||||
Sample |
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Keywords | ion channel / TRANSPORT PROTEIN | ||||||||||||
Function / homology | Function and homology information ATP transmembrane transporter activity / ATP transport / leak channel activity / Electric Transmission Across Gap Junctions / positive regulation of interleukin-1 alpha production / wide pore channel activity / bleb / monoatomic anion channel activity / monoatomic anion transmembrane transport / gap junction ...ATP transmembrane transporter activity / ATP transport / leak channel activity / Electric Transmission Across Gap Junctions / positive regulation of interleukin-1 alpha production / wide pore channel activity / bleb / monoatomic anion channel activity / monoatomic anion transmembrane transport / gap junction / gap junction channel activity / positive regulation of macrophage cytokine production / response to ATP / oogenesis / monoatomic cation transport / The NLRP3 inflammasome / positive regulation of interleukin-1 beta production / response to ischemia / calcium channel activity / calcium ion transport / actin filament binding / cell-cell signaling / scaffold protein binding / protease binding / transmembrane transporter binding / signaling receptor binding / endoplasmic reticulum membrane / structural molecule activity / endoplasmic reticulum / protein-containing complex / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.01 Å | ||||||||||||
Authors | Lu W / Du J | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nature / Year: 2020 Title: Structures of human pannexin 1 reveal ion pathways and mechanism of gating. Authors: Zheng Ruan / Ian J Orozco / Juan Du / Wei Lü / Abstract: Pannexin 1 (PANX1) is an ATP-permeable channel with critical roles in a variety of physiological functions such as blood pressure regulation, apoptotic cell clearance and human oocyte development. ...Pannexin 1 (PANX1) is an ATP-permeable channel with critical roles in a variety of physiological functions such as blood pressure regulation, apoptotic cell clearance and human oocyte development. Here we present several structures of human PANX1 in a heptameric assembly at resolutions of up to 2.8 angström, including an apo state, a caspase-7-cleaved state and a carbenoxolone-bound state. We reveal a gating mechanism that involves two ion-conducting pathways. Under normal cellular conditions, the intracellular entry of the wide main pore is physically plugged by the C-terminal tail. Small anions are conducted through narrow tunnels in the intracellular domain. These tunnels connect to the main pore and are gated by a long linker between the N-terminal helix and the first transmembrane helix. During apoptosis, the C-terminal tail is cleaved by caspase, allowing the release of ATP through the main pore. We identified a carbenoxolone-binding site embraced by W74 in the extracellular entrance and a role for carbenoxolone as a channel blocker. We identified a gap-junction-like structure using a glycosylation-deficient mutant, N255A. Our studies provide a solid foundation for understanding the molecular mechanisms underlying the channel gating and inhibition of PANX1 and related large-pore 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_21591.map.gz | 40.1 MB | EMDB map data format | |
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Header (meta data) | emd-21591-v30.xml emd-21591.xml | 13.9 KB 13.9 KB | Display Display | EMDB header |
Images | emd_21591.png | 129.8 KB | ||
Filedesc metadata | emd-21591.cif.gz | 5.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21591 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21591 | HTTPS FTP |
-Validation report
Summary document | emd_21591_validation.pdf.gz | 492.7 KB | Display | EMDB validaton report |
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Full document | emd_21591_full_validation.pdf.gz | 492.3 KB | Display | |
Data in XML | emd_21591_validation.xml.gz | 6.1 KB | Display | |
Data in CIF | emd_21591_validation.cif.gz | 6.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21591 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21591 | HTTPS FTP |
-Related structure data
Related structure data | 6wbkMC 6wbfC 6wbgC 6wbiC 6wblC 6wbmC 6wbnC C: citing same article (ref.) M: atomic model generated by this map |
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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_21591.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Unsharpened map of %u0394NTH/%u0394CTT-hsPANX1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.026 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 : Wild type human Pannexin 1 channel
Entire | Name: Wild type human Pannexin 1 channel |
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Components |
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-Supramolecule #1: Wild type human Pannexin 1 channel
Supramolecule | Name: Wild type human Pannexin 1 channel / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Pannexin-1
Macromolecule | Name: Pannexin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 41.946035 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAIAQLATEY VFSDFLLKEP TEPKFKGLRL ELAVDKMVTC IAVGLPLLLI SLAFAQEISI GTQISCFSPS SFSWRQAAFV DSYCWAAVQ QKNSLQSESG NLPLWLHKFF PYILLLFAIL LYLPPLFWRF AAAPHICSDL KFIMEELDKV YNRAIKAAKS A RDLDMRDG ...String: MAIAQLATEY VFSDFLLKEP TEPKFKGLRL ELAVDKMVTC IAVGLPLLLI SLAFAQEISI GTQISCFSPS SFSWRQAAFV DSYCWAAVQ QKNSLQSESG NLPLWLHKFF PYILLLFAIL LYLPPLFWRF AAAPHICSDL KFIMEELDKV YNRAIKAAKS A RDLDMRDG ACSVPGVTEN LGQSLWEVSE SHFKYPIVEQ YLKTKKNSNN LIIKYISCRL LTLIIILLAC IYLGYYFSLS SL SDEFVCS IKSGILRNDS TVPDQFQCKL IAVGIFQLLS VINLVVYVLL APVVVYTLFV PFRQKTDVLK VYEILPTFDV LHF KSEGYN DLSLYNLFLE ENISEVKSYK CLKVLENIKS SGQGIDPMLL LTNL UniProtKB: Pannexin-1 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 7 mg/mL |
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Buffer | pH: 8 |
Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 291.15 K / Instrument: FEI VITROBOT MARK III |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average exposure time: 8.0 sec. / Average electron dose: 49.6 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
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-6wbk: |