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- PDB-9t35: Cryo-EM structure of homo-hexameric hLRRC8A L402W -

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Basic information

Entry
Database: PDB / ID: 9t35
TitleCryo-EM structure of homo-hexameric hLRRC8A L402W
ComponentsVolume-regulated anion channel subunit LRRC8A
KeywordsMEMBRANE PROTEIN / volume-regulated anion channel
Function / homology
Function and homology information


pre-B cell differentiation / Miscellaneous transport and binding events / volume-sensitive anion channel activity / aspartate transmembrane transport / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane / monoatomic anion transmembrane transport / taurine transmembrane transport / cell volume homeostasis / monoatomic anion transport ...pre-B cell differentiation / Miscellaneous transport and binding events / volume-sensitive anion channel activity / aspartate transmembrane transport / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane / monoatomic anion transmembrane transport / taurine transmembrane transport / cell volume homeostasis / monoatomic anion transport / protein hexamerization / response to osmotic stress / monoatomic ion channel complex / positive regulation of myoblast differentiation / intracellular glucose homeostasis / chloride transmembrane transport / positive regulation of insulin secretion / spermatogenesis / lysosomal membrane / cell surface / membrane / identical protein binding / plasma membrane / cytoplasm
Similarity search - Function
LRRC8, pannexin-like TM region / Pannexin-like TM region of LRRC8 / : / : / Leucine-rich repeat region / Leucine-rich repeat, SDS22-like subfamily / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. ...LRRC8, pannexin-like TM region / Pannexin-like TM region of LRRC8 / : / : / Leucine-rich repeat region / Leucine-rich repeat, SDS22-like subfamily / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily
Similarity search - Domain/homology
Volume-regulated anion channel subunit LRRC8A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.78 Å
AuthorsBertelli, S. / Wang, L. / Klussendorf, M. / Pusch, M. / Dutzler, R. / Stauber, T.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation10.006.508 Switzerland
CitationJournal: To Be Published / Year: 2026
Title: The intracellular subdomain of the volume regulated anion channel subunit LRRC8A is a hotspot of channel activation
Authors: Bertelli, S. / Wang, L. / Klussendorf, M. / Pusch, M. / Dutzler, R. / Stauber, T.
History
DepositionOct 24, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 9, 2026Provider: repository / Type: Initial release
Revision 1.0Sep 9, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Volume-regulated anion channel subunit LRRC8A
B: Volume-regulated anion channel subunit LRRC8A
C: Volume-regulated anion channel subunit LRRC8A
D: Volume-regulated anion channel subunit LRRC8A
E: Volume-regulated anion channel subunit LRRC8A
F: Volume-regulated anion channel subunit LRRC8A


Theoretical massNumber of molelcules
Total (without water)566,5116
Polymers566,5116
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein
Volume-regulated anion channel subunit LRRC8A / Leucine-rich repeat-containing protein 8A / HsLRRC8A / Swelling protein 1


Mass: 94418.523 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LRRC8A, KIAA1437, LRRC8, SWELL1, UNQ221/PRO247 / Production host: Homo sapiens (human) / References: UniProt: Q8IWT6
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: the homo-hexamer hLRRC8A L402W / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8.5 / Details: 25 mM Tris pH 8.5, 250 mM NaCl, 0.01% GDN
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE-PROPANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 60.61 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.21.2_5419model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.78 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42551 / Symmetry type: POINT
RefinementHighest resolution: 2.78 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00215780
ELECTRON MICROSCOPYf_angle_d0.3521366
ELECTRON MICROSCOPYf_dihedral_angle_d9.9475664
ELECTRON MICROSCOPYf_chiral_restr0.0362358
ELECTRON MICROSCOPYf_plane_restr0.0022568

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