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- EMDB-21589: Cryo-EM structure of human Pannexin 1 channel with its C-terminal... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21589 | ||||||||||||
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Title | Cryo-EM structure of human Pannexin 1 channel with its C-terminal tail cleaved by caspase-7 | ||||||||||||
![]() | Unsharpened map of %u0394CTT-hsPANX1 | ||||||||||||
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Function / homology | ![]() ATP transmembrane transporter activity / ATP transport / Electric Transmission Across Gap Junctions / leak channel activity / positive regulation of interleukin-1 alpha production / bleb / wide pore channel activity / monoatomic anion channel activity / monoatomic anion transmembrane transport / gap junction ...ATP transmembrane transporter activity / ATP transport / Electric Transmission Across Gap Junctions / leak channel activity / positive regulation of interleukin-1 alpha production / bleb / wide pore channel activity / 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 | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.97 Å | ||||||||||||
![]() | Lu W / Du J / Ruan Z | ||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 40.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
Images | ![]() | 169.5 KB | ||
Others | ![]() | 7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wbgMC ![]() 6wbfC ![]() 6wbiC ![]() 6wbkC ![]() 6wblC ![]() 6wbmC ![]() 6wbnC C: citing same article ( M: atomic model generated by this map |
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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
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Unsharpened map of %u0394CTT-hsPANX1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Additional map: Sharpened map of %u0394CTT-hsPANX1
File | emd_21589_additional.map | ||||||||||||
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Annotation | Sharpened map of %u0394CTT-hsPANX1 | ||||||||||||
Projections & Slices |
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Density Histograms |
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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: #1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 42.247441 KDa |
Recombinant expression | Organism: ![]() |
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 LTNLGMI |
-Macromolecule #2: PHOSPHATIDYLETHANOLAMINE
Macromolecule | Name: PHOSPHATIDYLETHANOLAMINE / type: ligand / ID: 2 / Number of copies: 14 / Formula: PTY |
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Molecular weight | Theoretical: 734.039 Da |
Chemical component information | ![]() ChemComp-PTY: |
-Macromolecule #3: 1,2-Distearoyl-sn-glycerophosphoethanolamine
Macromolecule | Name: 1,2-Distearoyl-sn-glycerophosphoethanolamine / type: ligand / ID: 3 / Number of copies: 7 / Formula: 3PE |
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Molecular weight | Theoretical: 748.065 Da |
Chemical component information | ![]() ChemComp-3PE: |
-Macromolecule #4: DIACYL GLYCEROL
Macromolecule | Name: DIACYL GLYCEROL / type: ligand / ID: 4 / Number of copies: 7 / Formula: DGA |
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Molecular weight | Theoretical: 625.018 Da |
Chemical component information | ![]() ChemComp-DGA: |
-Macromolecule #5: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 14 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 7 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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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 |
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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) / 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: ![]() |
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 | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-6wbg: |