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Open data
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Basic information
| Entry | Database: PDB / ID: 9rgn | ||||||||||||||||||||||||||||||
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| Title | SsCl at pH 6.5 + IVM - Partially opened | ||||||||||||||||||||||||||||||
Components | pH gated chloride channel | ||||||||||||||||||||||||||||||
Keywords | MEMBRANE PROTEIN / Ion channel / pLGIC / pH-sensitive channel / Ivermectin | ||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationligand-gated monoatomic anion channel activity / chloride channel activity / extracellular ligand-gated monoatomic ion channel activity / transmembrane signaling receptor activity / plasma membrane Similarity search - Function | ||||||||||||||||||||||||||||||
| Biological species | Sarcoptes scabiei (arthropod) | ||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||||||||||||||||||||
Authors | Kleiz-Ferreira, J. / Brams, M. / Harrison, P.J. / Gallagher, C. / Nys, M. / Donze, Y. / Quigley, A. / Bertrand, D. / Ulens, C. | ||||||||||||||||||||||||||||||
| Funding support | Belgium, 2items
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Citation | Journal: Nat Commun / Year: 2026Title: Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite. Authors: Jessica Kleiz-Ferreira / Marijke Brams / Peter J Harrison / Casey I Gallagher / Mieke Nys / Ysaline Donze / Andrew Quigley / Daniel Bertrand / Chris Ulens / ![]() Abstract: Scabies is a skin infestation caused by the mite Sarcoptes scabiei and represents a substantial global health burden exacerbated by emerging resistance to ivermectin. An anionic pentameric ligand- ...Scabies is a skin infestation caused by the mite Sarcoptes scabiei and represents a substantial global health burden exacerbated by emerging resistance to ivermectin. An anionic pentameric ligand-gated ion channel from the mite, SsCl, shows pH-sensitivity and is significantly modulated by ivermectin. Here, we use cryo-EM and electrophysiology to explore the pH-sensing mechanisms of SsCl and the impact of ivermectin on channel activity. Structures of SsCl were resolved in closed (pH 6.5) and desensitized (pH 9) states, alongside ivermectin-bound conformations. The desensitized structure adopts an unexpected hourglass conformation, suggesting a gating mechanism closer related to cation-selective channels. Structural analysis and mutagenesis identify extracellular histidine and glutamic acid residues that impact the pH-sensitivity, likely contributing to a broader pH-sensing network. Ivermectin-bound structures reveal pH-dependent modulation, enhancing open-state prevalence at pH 9 and enabling atypical activation at pH 6.5. These findings offer initial insights into SsCl's pH-sensitivity and ivermectin's activity, informing next-generation antiparasitic design. | ||||||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9rgn.cif.gz | 355.4 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9rgn.ent.gz | 291.5 KB | Display | PDB format |
| PDBx/mmJSON format | 9rgn.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rg/9rgn ftp://data.pdbj.org/pub/pdb/validation_reports/rg/9rgn | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53951MC ![]() 9rgmC ![]() 9rgoC ![]() 9rgpC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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| 1 |
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Components
| #1: Protein | Mass: 39763.938 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Details: Truncated intracellular region, with a linker. / Source: (gene. exp.) Sarcoptes scabiei (arthropod) / Production host: ![]() #2: Chemical | ChemComp-IVM / ( Has ligand of interest | Y | Has protein modification | Y | |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Sarcoptes scabies chloride channel (SsCl) / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Sarcoptes scabiei (arthropod) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 6.5 |
| Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Instrument: LEICA PLUNGER / Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: OTHER / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
| Image recording | Electron dose: 1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: NONE | ||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 5506940 | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 344703 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Resolution: 3.1→134.3 Å / Cor.coef. Fo:Fc: 0.936
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| Displacement parameters | Biso mean: 124.277 Å2 | ||||||||||||||||||||||||
| LS refinement shell | Highest resolution: 3.1 Å /
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Sarcoptes scabiei (arthropod)
Belgium, 2items
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