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- EMDB-53952: SsCl at pH 9 - Desensitized -

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Basic information

Entry
Database: EMDB / ID: EMD-53952
TitleSsCl at pH 9 - Desensitized
Map dataSharp
Sample
  • Organelle or cellular component: Sarcoptes scabies chloride channel (SsCl)
    • Protein or peptide: pH gated chloride channel
  • Ligand: CHLORIDE ION
KeywordsIon channel / pLGIC / pH-sensitive channel / MEMBRANE PROTEIN
Function / homology
Function and homology information


ligand-gated monoatomic anion channel activity / chloride channel activity / extracellular ligand-gated monoatomic ion channel activity / transmembrane signaling receptor activity / plasma membrane
Similarity search - Function
Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel / Neurotransmitter-gated ion-channel ligand-binding domain / Neurotransmitter-gated ion-channel ligand-binding domain superfamily / Neurotransmitter-gated ion-channel ligand binding domain
Similarity search - Domain/homology
pH gated chloride channel
Similarity search - Component
Biological speciesSarcoptes scabiei (arthropod)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.14 Å
AuthorsKleiz-Ferreira J / Brams M / Harrison PJ / Gallagher C / Nys M / Donze Y / Quigley A / Bertrand D / Ulens C
Funding support Belgium, European Union, 3 items
OrganizationGrant numberCountry
KU LeuvenC14/23/128 Belgium
Research Foundation - Flanders (FWO)G087921N Belgium
iNEXT-DiscoveryPID 30222European Union
CitationJournal: Nat Commun / Year: 2026
Title: 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.
History
DepositionJun 6, 2025-
Header (metadata) releaseMar 18, 2026-
Map releaseMar 18, 2026-
UpdateMar 25, 2026-
Current statusMar 25, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_53952.png

Downloads & links

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Map

FileDownload / File: emd_53952.map.gz / Format: CCP4 / Size: 67 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharp
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 260 pix.
= 216.06 Å		0.83 Å/pix.
x 260 pix.
= 216.06 Å		0.83 Å/pix.
x 260 pix.
= 216.06 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.831 Å
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Contour LevelBy AUTHOR: 0.42
Minimum - Maximum-2.0010734 - 3.0397198
Average (Standard dev.)0.009241078 (±0.11330362)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions260260260
Spacing260260260
CellA=B=C: 216.06 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_53952_msk_1.map
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Additional map: Unsharpened

Fileemd_53952_additional_1.map
AnnotationUnsharpened
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Half map: HalfB

Fileemd_53952_half_map_1.map
AnnotationHalfB
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Half map: HalfA

Fileemd_53952_half_map_2.map
AnnotationHalfA
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Sample components

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Entire : Sarcoptes scabies chloride channel (SsCl)

EntireName: Sarcoptes scabies chloride channel (SsCl)
Components
  • Organelle or cellular component: Sarcoptes scabies chloride channel (SsCl)
    • Protein or peptide: pH gated chloride channel
  • Ligand: CHLORIDE ION

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Supramolecule #1: Sarcoptes scabies chloride channel (SsCl)

SupramoleculeName: Sarcoptes scabies chloride channel (SsCl) / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Sarcoptes scabiei (arthropod)

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Macromolecule #1: pH gated chloride channel

MacromoleculeName: pH gated chloride channel / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Sarcoptes scabiei (arthropod)
Molecular weightTheoretical: 34.992449 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: VIIDETFIKT FNKTDRLIRP SFNDKADVID VSMLIDRFAY YHDIESILEI QAQFEYHWFD QRVKFDCDRS SRIEGNHYHE QIWVPDLRV SRTEDIDVFE SENLTRLISI QIDCDGHVRM RFRSNLDLIC VMNYQNYPFD EQTCEIELIP SYMEINRLQL R WKDQNIMI ...String:
VIIDETFIKT FNKTDRLIRP SFNDKADVID VSMLIDRFAY YHDIESILEI QAQFEYHWFD QRVKFDCDRS SRIEGNHYHE QIWVPDLRV SRTEDIDVFE SENLTRLISI QIDCDGHVRM RFRSNLDLIC VMNYQNYPFD EQTCEIELIP SYMEINRLQL R WKDQNIMI RDDFYMSGHL LKGYSVHQKD VELMPYNEIY SALFVHLHLK RQFIYHILVL FLPSIFIVLT SWISFWICIP AR VTLCVTT LLAMVTVSKE SKQNIPKVPY VKAVDLWFAG CIVSIFITLI EYIFVC

UniProtKB: pH gated chloride channel

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Macromolecule #2: CHLORIDE ION

MacromoleculeName: CHLORIDE ION / type: ligand / ID: 2 / Number of copies: 1 / Formula: CL
Molecular weightTheoretical: 35.453 Da

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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 mg/mL
BufferpH: 9
VitrificationCryogen name: ETHANE / Instrument: LEICA PLUNGER

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 7779179
CTF correctionSoftware - Name: CTFFIND / Type: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 186182
Initial angle assignmentType: OTHER / Software - Name: RELION (ver. 5)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
FSC plot (resolution estimation)

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