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- EMDB-21597: Cryo-EM structure of wild type human Pannexin 1 channel in the pr... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21597 | ||||||||||||
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Title | Cryo-EM structure of wild type human Pannexin 1 channel in the presence of 150 mM KCl | ||||||||||||
![]() | Unsharpened map of K -wt-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: 3.15 Å | ||||||||||||
![]() | Lu W / Du J | ||||||||||||
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 | ![]() | 40.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16 KB 16 KB | Display Display | ![]() |
Images | ![]() | 168 KB | ||
Others | ![]() | 6.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wbfC ![]() 6wbgC ![]() 6wbiC ![]() 6wbkC ![]() 6wblC ![]() 6wbmC ![]() 6wbnC C: citing same article ( |
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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
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Annotation | Unsharpened map of K -wt-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 K -wt-hsPANX1
File | emd_21597_additional_1.map | ||||||||||||
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Annotation | Sharpened map of K -wt-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: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Pannexin-1
Macromolecule | Name: Pannexin-1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: MAIAQLATEY VFSDFLLKEP TEPKFKGLRL ELAVDKMVTC IAVGLPLLLI SLAFAQEISI GTQISCFSP SSFSWRQAAF VDSYCWAAVQ QKNSLQSESG NLPLWLHKFF PYILLLFAIL L YLPPLFWR FAAAPHICSD LKFIMEELDK VYNRAIKAAK SARDLDMRDG ...String: MAIAQLATEY VFSDFLLKEP TEPKFKGLRL ELAVDKMVTC IAVGLPLLLI SLAFAQEISI GTQISCFSP SSFSWRQAAF VDSYCWAAVQ QKNSLQSESG NLPLWLHKFF PYILLLFAIL L YLPPLFWR FAAAPHICSD LKFIMEELDK VYNRAIKAAK SARDLDMRDG ACSVPGVTEN LG QSLWEVS ESHFKYPIVE QYLKTKKNSN NLIIKYISCR LLTLIIILLA CIYLGYYFSL SSL SDEFVC SIKSGILRND STVPDQFQCK LIAVGIFQLL SVINLVVYVL LAPVVVYTLF VPFR QKTDV LKVYEILPTF DVLHFKSEGY NDLSLYNLFL EENISEVKSY KCLKVLENIK SSGQG IDPM LLLTNLGMI(PTY) (PTY)(PEH)(DGA)(CLR)(CLR)(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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