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- EMDB-55591: Structure of heteromeric mouse LRRC8A/D Volume-Regulated Anion Ch... -

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Basic information

Entry
Database: EMDB / ID: EMD-55591
TitleStructure of heteromeric mouse LRRC8A/D Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1, Conformation 2
Map data
Sample
  • Complex: Heteromeric LRRC8A/D in complex with Sb1, conformation 2
    • Protein or peptide: Volume-regulated anion channel subunit LRRC8A
    • Protein or peptide: Synthetic Nanobody Sb1
    • Protein or peptide: Volume-regulated anion channel subunit LRRC8D
KeywordsHeteromeric LRRC8 protein / cell swelling / MEMBRANE PROTEIN
Function / homology
Function and homology information


Miscellaneous transport and binding events / pre-B cell differentiation / 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 ...Miscellaneous transport and binding events / pre-B cell differentiation / 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 / cellular response to osmotic stress / 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 / endoplasmic reticulum 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 / Volume-regulated anion channel subunit LRRC8D
Similarity search - Component
Biological speciesMus musculus (house mouse) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.16 Å
AuthorsLehmann EF / Deneka D / Stierli F / Rutz S / Dutzler R
Funding support Switzerland, 1 items
OrganizationGrant numberCountry
Swiss National Science Foundation Switzerland
CitationJournal: To Be Published
Title: Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions
Authors: Lehmann EF / Deneka D / Stierli F / Rutz S / Dutzler R
History
DepositionNov 5, 2025-
Header (metadata) releaseSep 2, 2026-
Map releaseSep 2, 2026-
UpdateSep 2, 2026-
Current statusSep 2, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_55591.map.gz / Format: CCP4 / Size: 187 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)X (Row.)Y (Col.)
1.3 Å/pix.
x 366 pix.
= 476.532 Å
1.3 Å/pix.
x 366 pix.
= 476.532 Å
1.3 Å/pix.
x 366 pix.
= 476.532 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.302 Å
Density
Contour LevelBy AUTHOR: 0.0855
Minimum - Maximum-0.5211983 - 1.4157397
Average (Standard dev.)0.0005628791 (±0.022602908)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderYXZ
Origin000
Dimensions366366366
Spacing366366366
CellA=B=C: 476.532 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_55591_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_55591_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Heteromeric LRRC8A/D in complex with Sb1, conformation 2

EntireName: Heteromeric LRRC8A/D in complex with Sb1, conformation 2
Components
  • Complex: Heteromeric LRRC8A/D in complex with Sb1, conformation 2
    • Protein or peptide: Volume-regulated anion channel subunit LRRC8A
    • Protein or peptide: Synthetic Nanobody Sb1
    • Protein or peptide: Volume-regulated anion channel subunit LRRC8D

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Supramolecule #1: Heteromeric LRRC8A/D in complex with Sb1, conformation 2

SupramoleculeName: Heteromeric LRRC8A/D in complex with Sb1, conformation 2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Volume-regulated anion channel subunit LRRC8A

MacromoleculeName: Volume-regulated anion channel subunit LRRC8A / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 95.127391 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSIPVTELRY FADTQPAYRI LKPWWDVFTD YISIVMLMIA VFGGTLQVTQ DKMICLPCKW VTKDSCNDSF RGWAASSPEP TYPNSTVLP TPDTGPTGIK YDLDRHQYNY VDAVCYENRL HWFAKYFPYL VLLHTLIFLA CSNFWFKFPR TSSKLEHFVS I LLKCFDSP ...String:
MSIPVTELRY FADTQPAYRI LKPWWDVFTD YISIVMLMIA VFGGTLQVTQ DKMICLPCKW VTKDSCNDSF RGWAASSPEP TYPNSTVLP TPDTGPTGIK YDLDRHQYNY VDAVCYENRL HWFAKYFPYL VLLHTLIFLA CSNFWFKFPR TSSKLEHFVS I LLKCFDSP WTTRALSETV VEESDPKPAF SKMNGSMDKK SSTVSEDVEA TVPMLQRTKS RIEQGIVDRS ETGVLDKKEG EQ AKALFEK VKKFRTHVEE GDIVYRLYMR QTIIKVIKFA LIICYTVYYV HNIKFDVDCT VDIESLTGYR TYRCAHPLAT LFK ILASFY ISLVIFYGLI CMYTLWWMLR RSLKKYSFES IREESSYSDI PDVKNDFAFM LHLIDQYDPL YSKRFAVFLS EVSE NKLRQ LNLNNEWTLD KLRQRLTKNA QDKLELHLFM LSGIPDTVFD LVELEVLKLE LIPDVTIPPS IAQLTGLKEL WLYHT AAKI EAPALAFLRE NLRALHIKFT DIKEIPLWIY SLKTLEELHL TGNLSAENNR YIVIDGLREL KRLKVLRLKS NLSKLP QVV TDVGVHLQKL SINNEGTKLI VLNSLKKMVN LTELELIRCD LERIPHSIFS LHNLQEIDLK DNNLKTIEEI ISFQHLH RL TCLKLWYNHI AYIPIQIGNL TNLERLYLNR NKIEKIPTQL FYCRKLRYLD LSHNNLTFLP ADIGLLQNLQ NLAVTANR I EALPPELFQC RKLRALHLGN NVLQSLPSRV GELTNLTQIE LRGNRLECLP VELGECPLLK RSGLVVEEDL FSTLPPEVK ERLWRADKEQ AALEVLFQ

UniProtKB: Volume-regulated anion channel subunit LRRC8A

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Macromolecule #2: Synthetic Nanobody Sb1

MacromoleculeName: Synthetic Nanobody Sb1 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 13.115529 KDa
Recombinant expressionOrganism: Escherichia coli MC1061 (bacteria)
SequenceString:
GPSQVQLVES GGGLVQAGGS LRLSCAASGF PVGRHFMYWY RQAPGKEREW VAAIYSYGEY TEYADSVKGR FTISRDNAKN TVYLQMNSL KPEDTAVYYC YVYVGNEYWG QGTQVTVSA

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Macromolecule #3: Volume-regulated anion channel subunit LRRC8D

MacromoleculeName: Volume-regulated anion channel subunit LRRC8D / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 105.429789 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSFTLAEVAS LNDIQPTYRI LKPWWDVFMD YLAVVMLMVA IFAGTMQLTK DQVVCLPVLP SPANSKAHTP PGNADVTTEV PRMETATHQ DQNGQTTTND VAFGTSAVTP DIPLQATHPH AESTLPNQEV KKEKRDPTGR KTNLDFQQYV FINQMCYHLA L PWYSKYFP ...String:
MSFTLAEVAS LNDIQPTYRI LKPWWDVFMD YLAVVMLMVA IFAGTMQLTK DQVVCLPVLP SPANSKAHTP PGNADVTTEV PRMETATHQ DQNGQTTTND VAFGTSAVTP DIPLQATHPH AESTLPNQEV KKEKRDPTGR KTNLDFQQYV FINQMCYHLA L PWYSKYFP YLALIHTIIL MVSSNFWFKY PKTCSKVEHF VSILGKCFES PWTTKALSET ACEDSEENKQ RITGAQTLPK HV STSSDEG SPSASTPMIN KTGFKFSAEK PVIEVPSMTI LDKKDGEQAK ALFEKVRKFR AHVEDSDLIY KLYVVQTVIK TAK FIFILC YTANFVNAIS FEHVCKPKVE HLIGYEVFEC THNMAYMLKK LLISYISIIC VYGFICLYTL FWLFRIPLKE YSFE KVREE SSFSDIPDVK NDFAFLLHMV DQYDQLYSKR FGVFLSEVSE NKLREISLNH EWTFEKLRQH VSRNAQDKQE LHLFM LSGV PDAVFDLTDL DVLKLELIPE AKIPAKISQM TNLQELHLCH CPAKVEQTAF SFLRDHLRCL HVKFTDVAEI PAWVYL LKN LRELYLIGNL NSENNKMIGL ESLRELRHLK ILHVKSNLTK VPSNITDVAP HLTKLVIHND GTKLLVLNSL KKMMNVA EL ELQNCELERI PHAIFSLSNL QELDLKSNNI RTIEEIISFQ HLKRLTCLKL WHNKIVAIPP SITHVKNLES LYFSNNKL E SLPTAVFSLQ KLRCLDVSYN NISTIPIEIG LLQNLQHLHI TGNKVDILPK QLFKCVKLRT LNLGQNCIAS LPEKISQLT QLTQLELKGN CLDRLPAQLG QCRMLKKSGL VVEDQLFDTL PLEVKEALNQ DVNVPFANGI ALEVLFQGPQ GTEQKLISEE DLRGASMDE KTTGWRGGHV VEGLAGELEQ LRARLEHHPQ GQREP

UniProtKB: Volume-regulated anion channel subunit LRRC8D

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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

BufferpH: 8.5
VitrificationCryogen name: ETHANE-PROPANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 63.03 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.16 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 266318
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

Chain - Source name: PDB / Chain - Initial model type: experimental model
Output model

PDB-9t5o:
Structure of heteromeric mouse LRRC8A/D Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1, Conformation 2

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