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Yorodumi- EMDB-70873: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alp... -
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Open data
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Basic information
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| Title | Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA and PZ-II-029 | |||||||||
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Keywords | neurotransmitter receptor / cys-loop receptor / ligand-gated ion channel / MEMBRANE PROTEIN | |||||||||
| Function / homology | Function and homology informationdiazepam binding / inhibitory extracellular ligand-gated monoatomic ion channel activity / GABA receptor activation / response to methamphetamine hydrochloride / inhibitory synapse / response to auditory stimulus / GABA receptor complex / cellular response to histamine / inner ear receptor cell development / inhibitory synapse assembly ...diazepam binding / inhibitory extracellular ligand-gated monoatomic ion channel activity / GABA receptor activation / response to methamphetamine hydrochloride / inhibitory synapse / response to auditory stimulus / GABA receptor complex / cellular response to histamine / inner ear receptor cell development / inhibitory synapse assembly / GABA-gated chloride ion channel activity / GABA-A receptor complex / GABA-A receptor activity / innervation / chloride transport / response to anesthetic / postsynaptic specialization membrane / gamma-aminobutyric acid signaling pathway / synaptic transmission, GABAergic / adult behavior / cellular response to zinc ion / chloride channel activity / cochlea development / chloride channel complex / neuron development / presynaptic active zone membrane / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / chloride transmembrane transport / cytoplasmic vesicle membrane / post-embryonic development / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / GABA-ergic synapse / dendritic spine / response to ethanol / chemical synaptic transmission / postsynaptic membrane / postsynapse / axon / glutamatergic synapse / cell surface / plasma membrane Similarity search - Function | |||||||||
| Biological species | ![]() ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.74 Å | |||||||||
Authors | Sun C / Gouaux E | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2026Title: Molecular assemblies and pharmacology of cerebellar GABA receptors. Authors: Chang Sun / Jennifer N Jahncke / Kevin M Wright / Eric Gouaux / ![]() Abstract: GABA receptors (GABARs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although α1-containing GABARs are ...GABA receptors (GABARs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although α1-containing GABARs are broadly expressed and are pharmacologically important, the molecular diversity of native α1-based assemblies in specific brain regions remains incompletely understood. Here, we use immunofluorescence, mass spectrometry, and cryogenic electron microscopy (cryo-EM) to characterize the spatial distribution, subunit composition, and structural architecture of native α1-containing GABARs in the rat cerebellum. Confocal microscopy reveals robust colocalization of α1 and γ2 subunits across cerebellar layers, including prominent labeling at glomerular synapses. Biochemical purification and proteomic analysis identify a range of α, β, and γ subunits, along with abundant α6 and δ subunits. Using cryo-EM and automated subunit identification, we resolve eight α1-containing receptor assemblies, including the first structure of α6-containing receptors. We further determine the binding mode of the α6-selective pyrazoloquinolinone modulator PZ-II-029 at the α/γ interface, showing ligand-induced expansion of the entire extracellular domain (ECD). Together, our study defines the structure and subunit composition of the α1-containing cerebellar GABARs and elaborates the molecular interactions between native receptors and pyrazoloquinolinone, thereby laying the groundwork for brain region and subunit-specific pharmacology. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_70873.map.gz | 89.6 MB | EMDB map data format | |
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| Header (meta data) | emd-70873-v30.xml emd-70873.xml | 23.9 KB 23.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_70873_fsc.xml | 11.9 KB | Display | FSC data file |
| Images | emd_70873.png | 145.4 KB | ||
| Filedesc metadata | emd-70873.cif.gz | 7.5 KB | ||
| Others | emd_70873_additional_1.map.gz emd_70873_half_map_1.map.gz emd_70873_half_map_2.map.gz | 151.6 MB 165.3 MB 165.2 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-70873 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-70873 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9ounMC ![]() 9oumC ![]() 9ouoC ![]() 9oupC ![]() 9ouqC ![]() 9ourC ![]() 9ov4C M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_70873.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.956 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: map sharpened with EMReady
| File | emd_70873_additional_1.map | ||||||||||||
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| Annotation | map sharpened with EMReady | ||||||||||||
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-Half map: #2
| File | emd_70873_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_70873_half_map_2.map | ||||||||||||
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Sample components
-Entire : Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alp...
| Entire | Name: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA and PZ-II-029 |
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| Components |
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-Supramolecule #1: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alp...
| Supramolecule | Name: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA and PZ-II-029 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 350 KDa |
-Macromolecule #1: Gamma-aminobutyric acid receptor subunit gamma-2
| Macromolecule | Name: Gamma-aminobutyric acid receptor subunit gamma-2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 54.136945 KDa |
| Sequence | String: MSSPNTWSTG STVYSPVFSQ KMTLWILLLL SLYPGFTSQK SDDDYEDYAS NKTWVLTPKV PEGDVTVILN NLLEGYDNKL RPDIGVKPT LIHTDMYVNS IGPVNAINME YTIDIFFAQT WYDRRLKFNS TIKVLRLNSN MVGKIWIPDT FFRNSKKADA H WITTPNRM ...String: MSSPNTWSTG STVYSPVFSQ KMTLWILLLL SLYPGFTSQK SDDDYEDYAS NKTWVLTPKV PEGDVTVILN NLLEGYDNKL RPDIGVKPT LIHTDMYVNS IGPVNAINME YTIDIFFAQT WYDRRLKFNS TIKVLRLNSN MVGKIWIPDT FFRNSKKADA H WITTPNRM LRIWNDGRVL YTLRLTIDAE CQLQLHNFPM DEHSCPLEFS SYGYPREEIV YQWKRSSVEV GDTRSWRLYQ FS FVGLRNT TEVVKTTSGD YVVMSVYFDL SRRMGYFTIQ TYIPCTLIVV LSWVSFWINK DAVPARTSLG ITTVLTMTTL STI ARKSLP KVSYVTAMDL FVSVCFIFVF SALVEYGTLH YFVSNRKPSK DKDKKKKNPA PTIDIRPRSA TIQMNNATHL QERD EEYGY ECLDGKDCAS FFCCFEDCRT GAWRHGRIHI RIAKMDSYAR IFFPTAFCLF NLVYWVSYLY L UniProtKB: Gamma-aminobutyric acid receptor subunit gamma-2 |
-Macromolecule #2: 8E3 Fab heavy chain
| Macromolecule | Name: 8E3 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 24.159895 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: EIQLQQSGPE LVKPGTSVKV SCKASGYSFT DYNMYWVKQS HGKSLEWIGY IDPYNADTTY NREFKGKATL TVDKSSSTAF MHLNSLTSE DSAVYYCARK RNNFYFDYWG QGTPLTVSSA KTTPPSVYPL APGCGDTTGS SVTLGCLVKG YFPESVTVTW N SGSLSSSV ...String: EIQLQQSGPE LVKPGTSVKV SCKASGYSFT DYNMYWVKQS HGKSLEWIGY IDPYNADTTY NREFKGKATL TVDKSSSTAF MHLNSLTSE DSAVYYCARK RNNFYFDYWG QGTPLTVSSA KTTPPSVYPL APGCGDTTGS SVTLGCLVKG YFPESVTVTW N SGSLSSSV HTFPALLQSG LYTMSSSVTV PSSTWPSQTV TCSVAHPASS TTVDKKSAAL EVLFQ |
-Macromolecule #3: 8E3 Fab light chain
| Macromolecule | Name: 8E3 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 23.62408 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: YIVMTQSPKS MSMSLGERVT LSCRASEYVG SYVSWYQQKP EQSPKLLIYG ASNRYTGVPD RFAGSGSATD FTLTITSVQA EDLADYHCG QTYNYPTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK ...String: YIVMTQSPKS MSMSLGERVT LSCRASEYVG SYVSWYQQKP EQSPKLLIYG ASNRYTGVPD RFAGSGSATD FTLTITSVQA EDLADYHCG QTYNYPTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK DSTYSMSSTL TLTKDEYERH NSYTCEATHK TSTSPIVKSF NRNEC |
-Macromolecule #4: Gamma-aminobutyric acid receptor subunit alpha-1
| Macromolecule | Name: Gamma-aminobutyric acid receptor subunit alpha-1 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 51.818516 KDa |
| Sequence | String: MKKSRGLSDY LWAWTLILST LSGRSYGQPS QDELKDNTTV FTRILDRLLD GYDNRLRPGL GERVTEVKTD IFVTSFGPVS DHDMEYTID VFFRQSWKDE RLKFKGPMTV LRLNNLMASK IWTPDTFFHN GKKSVAHNMT MPNKLLRITE DGTLLYTMRL T VRAECPMH ...String: MKKSRGLSDY LWAWTLILST LSGRSYGQPS QDELKDNTTV FTRILDRLLD GYDNRLRPGL GERVTEVKTD IFVTSFGPVS DHDMEYTID VFFRQSWKDE RLKFKGPMTV LRLNNLMASK IWTPDTFFHN GKKSVAHNMT MPNKLLRITE DGTLLYTMRL T VRAECPMH LEDFPMDAHA CPLKFGSYAY TRAEVVYEWT REPARSVVVA EDGSRLNQYD LLGQTVDSGI VQSSTGEYVV MT THFHLKR KIGYFVIQTY LPCIMTVILS QVSFWLNRES VPARTVFGVT TVLTMTTLSI SARNSLPKVA YATAMDWFIA VCY AFVFSA LIEFATVNYF TKRGYAWDGK SVVPEKPKKV KDPLIKKNNT YAPTATSYTP NLARGDPGLA TIAKSATIEP KEVK PETKP PEPKKTFNSV SKIDRLSRIA FPLLFGIFNL VYWATYLNRE PQLKAPTPHQ UniProtKB: Gamma-aminobutyric acid receptor subunit alpha-1 |
-Macromolecule #5: Gamma-aminobutyric acid receptor subunit beta-2
| Macromolecule | Name: Gamma-aminobutyric acid receptor subunit beta-2 / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 54.697297 KDa |
| Sequence | String: MWRVRKRGYF GIWSFPLIIA AVCAQSVNDP SNMSLVKETV DRLLKGYDIR LRPDFGGPPV AVGMNIDIAS IDMVSEVNMD YTLTMYFQQ AWRDKRLSYN VIPLNLTLDN RVADQLWVPD TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA C MMDLRRYP ...String: MWRVRKRGYF GIWSFPLIIA AVCAQSVNDP SNMSLVKETV DRLLKGYDIR LRPDFGGPPV AVGMNIDIAS IDMVSEVNMD YTLTMYFQQ AWRDKRLSYN VIPLNLTLDN RVADQLWVPD TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA C MMDLRRYP LDEQNCTLEI ESYGYTTDDI EFYWRGDDNA VTGVTKIELP QFSIVDYKLI TKKVVFSTGS YPRLSLSFKL KR NIGYFIL QTYMPSILIT ILSWVSFWIN YDASAARVAL GITTVLTMTT INTHLRETLP KIPYVKAIDM YLMGCFVFVF MAL LEYALV NYIFFGRGPQ RQKKAAEKAA NANNEKMRLD VNKMDPHENI LLSTLEIKNE MATSEAVMGL GDPRSTMLAY DASS IQYRK AGLPRHSFGR NALERHVAQK KSRLRRRASQ LKITIPDLTD VNAIDRWSRI FFPVVFSFFN IVYWLYYVN UniProtKB: Gamma-aminobutyric acid receptor subunit beta-2 |
-Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
| Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 1 / Formula: NAG |
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| Molecular weight | Theoretical: 221.208 Da |
| Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #11: GAMMA-AMINO-BUTANOIC ACID
| Macromolecule | Name: GAMMA-AMINO-BUTANOIC ACID / type: ligand / ID: 11 / Number of copies: 2 / Formula: ABU |
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| Molecular weight | Theoretical: 103.12 Da |
| Chemical component information | ![]() ChemComp-ABU: |
-Macromolecule #12: 7-methoxy-2-(4-methoxyphenyl)-1,2-dihydro-3H-pyrazolo[4,3-c]quino...
| Macromolecule | Name: 7-methoxy-2-(4-methoxyphenyl)-1,2-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one type: ligand / ID: 12 / Number of copies: 1 / Formula: A1CEP |
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| Molecular weight | Theoretical: 321.33 Da |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 0.05 mg/mL |
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| Buffer | pH: 8 |
| Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 45.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Keywords
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

