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- EMDB-56448: Cryo-EM structure of mouse Pannexin 1 in complex with a ligand -

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Basic information

Entry
Database: EMDB / ID: EMD-56448
TitleCryo-EM structure of mouse Pannexin 1 in complex with a ligand
Map dataUnsharpened map
Sample
  • Complex: Mouse Pannexin 1 in complex with a ligand
KeywordsIon channel / DEL ligand / MEMBRANE PROTEIN
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.5 Å
AuthorsDrulyte I
Funding support1 items
OrganizationGrant numberCountry
Not funded
Citation
Journal: Sci Rep / Year: 2026
Title: Discovery of membrane channel modulators via DNA encoded library screening using native like membrane protein nanoparticles.
Authors: Francesco V Reddavide / Trine L Toft-Bertelsen / Ieva Drulyte / Aspen Rene Gutgsell / Dzung Nguyen / Sara Bonetti / Katerina Vafia / Anne-Sophie Tournillon / Stephan Heiden / Daniel Grosser ...Authors: Francesco V Reddavide / Trine L Toft-Bertelsen / Ieva Drulyte / Aspen Rene Gutgsell / Dzung Nguyen / Sara Bonetti / Katerina Vafia / Anne-Sophie Tournillon / Stephan Heiden / Daniel Grosser / Katarina Iric / Veronica Diez / Nanna MacAulay / Stefan Geschwindner / Michael Thompson / Jens Frauenfeld / Robin Löving /
Abstract: Developing novel drugs against membrane proteins is a major challenge in drug discovery due to the difficulty of stabilizing these targets for high-throughput screenings. Pannexin 1 (PANX1) is a ...Developing novel drugs against membrane proteins is a major challenge in drug discovery due to the difficulty of stabilizing these targets for high-throughput screenings. Pannexin 1 (PANX1) is a membrane channel protein involved in various physiological and pathological processes, making it a promising target for drug discovery. However, efforts to develop PANX1-targeting therapeutics have been hindered by the inherent challenges of stabilizing the protein channel and conducting effective pharmacological screening. Here, we report a proof-of-concept workflow that integrates the Salipro lipid nanoparticle platform with DNA-Encoded Library screenings in a detergent-free format. In this case study, the Salipro DirectMX method was used to generate functional PANX1 nanoparticles for drug discovery and characterisation. Using a high-stringency selection strategy and computational approaches, we identified a specific set of candidate compounds with selective PANX1 enrichment. Surface Plasmon Resonance analysis confirmed the identification of hit compounds. Cryo-Electron Microscopy of the Salipro-PANX1-Compound complex provided structural insights into a potential compound binding site. Electrophysiological recordings in PANX1-expressing Xenopus laevis oocytes demonstrated dose-dependent inhibition of PANX1-mediated ion conductance by the compounds. These findings establish a robust workflow for ligand discovery against challenging membrane protein targets and provide novel chemical starting points for the development of PANX1 modulators.
#1: Journal: Biorxiv / Year: 2026
Title: Discovery of Membrane Channel Modulators via DNA-Encoded Library Screening Using Native-Like Membrane Protein Nanoparticles
Authors: Reddavide FV / Toft-Bertelsen TL / Drulyte I / Gutgsell AR / Nguyen D / Bonetti S / Vafia K / Tournillon AS / Heiden S / Grosser D / Iric K / Diez V / MacAulay N / Geschwindner S / Thompson ...Authors: Reddavide FV / Toft-Bertelsen TL / Drulyte I / Gutgsell AR / Nguyen D / Bonetti S / Vafia K / Tournillon AS / Heiden S / Grosser D / Iric K / Diez V / MacAulay N / Geschwindner S / Thompson M / Frauenfeld J / Loving R
History
DepositionJan 21, 2026-
Header (metadata) releaseMar 4, 2026-
Map releaseMar 4, 2026-
UpdateJul 1, 2026-
Current statusJul 1, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_56448.png

Downloads & links

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Map

FileDownload / File: emd_56448.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationUnsharpened map
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.38 Å/pix.
x 160 pix.
= 221.536 Å		1.38 Å/pix.
x 160 pix.
= 221.536 Å		1.38 Å/pix.
x 160 pix.
= 221.536 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.3846 Å
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Histogram (log scale)
Contour LevelBy AUTHOR: 0.008
Minimum - Maximum-0.010965236 - 0.028910924
Average (Standard dev.)0.0003862935 (±0.0021061285)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions160160160
Spacing160160160
CellA=B=C: 221.53601 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_56448_msk_1.map
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Additional map: Post-processed masked & sharpened map

Fileemd_56448_additional_1.map
AnnotationPost-processed masked & sharpened map
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Additional map: Relion locres filtered map

Fileemd_56448_additional_2.map
AnnotationRelion_locres_filtered map
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Half map: Half map B

Fileemd_56448_half_map_1.map
AnnotationHalf map B
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Half map: Half map A

Fileemd_56448_half_map_2.map
AnnotationHalf map A
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Sample components

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Entire : Mouse Pannexin 1 in complex with a ligand

EntireName: Mouse Pannexin 1 in complex with a ligand
Components
  • Complex: Mouse Pannexin 1 in complex with a ligand

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Supramolecule #1: Mouse Pannexin 1 in complex with a ligand

SupramoleculeName: Mouse Pannexin 1 in complex with a ligand / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 350 KDa

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration2.5 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
50.0 mMHEPESN-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid
150.0 mMNaClsodium chloride
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
Details: Quantifoil R 1.2/1.3 Ultrathin Carbon grids were glow-discharged using 5 mA current for 30 s (GloQube, Quorum Technologies).
VitrificationCryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV
Details: To overcome preferred orientation, 0.5 mM fluorinated Fos-Choline 8 was added to the sample just before the grid freezing. Blot parameter: blot force 0, blot time 5 s, waiting time 30s..
DetailsCompound 6 was added to purified Salipro-mPANX1 particles at a final concentration of 500 uM.

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Electron microscopy

MicroscopeTFS GLACIOS
Specialist opticsEnergy filter - Name: TFS Selectris / Energy filter - Slit width: 10 eV
DetailsData was collected in EFTEM mode using 10 eV slit and a nominal magnification of 165,000, resulting in a calibrated pixel size of 0.694 A.
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 49.8 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 30.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.75 µm / Nominal magnification: 165000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN

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Image processing

CTF correctionSoftware - Name: RELION / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: EMDB MAP
EMDB ID:

15110

Final reconstructionApplied symmetry - Point group: C7 (7 fold cyclic) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 327491
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
FSC plot (resolution estimation)

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