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        <sites>
            <deposition>PDBe</deposition>
            <last_processing>PDBe</last_processing>
        </sites>
        <key_dates>
            <deposition>2018-10-08</deposition>
            <header_release>2018-11-07</header_release>
            <map_release>2019-01-02</map_release>
            <update>2025-10-01</update>
        </key_dates>
        <grant_support>
            <grant_reference>
                <funding_body>Medical Research Council (United Kingdom)</funding_body>
                <code>MR/L009609/1</code>
                <country>United Kingdom</country>
            </grant_reference>
            <grant_reference>
                <funding_body>Medical Research Council (United Kingdom)</funding_body>
                <code>MC_UP_1201/15</code>
                <country>United Kingdom</country>
            </grant_reference>
            <grant_reference>
                <funding_body>Medical Research Council (United Kingdom)</funding_body>
                <code>MC_UP_A025_1013</code>
                <country>United Kingdom</country>
            </grant_reference>
            <grant_reference>
                <funding_body>Biotechnology and Biological Sciences Research Council</funding_body>
                <code>BB/M024709/1</code>
                <country>United Kingdom</country>
            </grant_reference>
            <grant_reference>
                <funding_body>Cancer Research UK</funding_body>
                <code>C20724/A14414</code>
                <country>United Kingdom</country>
            </grant_reference>
            <grant_reference>
                <funding_body>Human Frontier Science Program</funding_body>
                <code>RGP0065/2014</code>
                <country>United Kingdom</country>
            </grant_reference>
            <grant_reference>
                <funding_body>Swiss National Science Foundation</funding_body>
                <code>168735</code>
                <country>Switzerland</country>
            </grant_reference>
            <grant_reference>
                <funding_body>National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)</funding_body>
                <code>GM 58448</code>
                <country>United States</country>
            </grant_reference>
        </grant_support>
        <title>CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with bicuculline and megabody Mb38.</title>
        <authors_list>
            <author>Masiulis S</author>
            <author>Desai R</author>
        </authors_list>
        <keywords>GABAAR, Membrane, Channel, Nanobody, Megabody, Cys-loop, PLGIC, Inhibition, Signalling, CNS, Neurons, Chloride, Ion, GABA, BCC, Bicuculline, MEMBRANE PROTEIN, Antagonist</keywords>
    </admin>
    <crossreferences>
        <citation_list>
            <primary_citation>
                <journal_citation published="true">
                    <author order="1">Masiulis S</author>
                    <author order="2">Desai R</author>
                    <author order="3">Uchanski T</author>
                    <author order="4">Serna Martin I</author>
                    <author order="5">Laverty D</author>
                    <author order="6">Karia D</author>
                    <author order="7">Malinauskas T</author>
                    <author order="8">Zivanov J</author>
                    <author order="9">Pardon E</author>
                    <author order="10">Kotecha A</author>
                    <author order="11">Steyaert J</author>
                    <author order="12">Miller KW</author>
                    <author order="13">Aricescu AR</author>
                    <title>GABAAreceptor signalling mechanisms revealed by structural pharmacology.</title>
                    <journal_abbreviation>Nature</journal_abbreviation>
                    <country>UK</country>
                    <volume>565</volume>
                    <first_page>454</first_page>
                    <last_page>459</last_page>
                    <year>2019</year>
                    <external_references type="PUBMED">30602790</external_references>
                    <external_references type="DOI">doi:10.1038/s41586-018-0832-5</external_references>
                    <external_references type="ISSN">0028-0836</external_references>
                    <external_references type="CSD">0006</external_references>
                    <external_references type="ASTM">NATUAS</external_references>
                </journal_citation>
            </primary_citation>
        </citation_list>
        <pdb_list>
            <pdb_reference>
                <pdb_id>6huk</pdb_id>
                <relationship>
                    <in_frame>FULLOVERLAP</in_frame>
                </relationship>
            </pdb_reference>
        </pdb_list>
        <other_db_list>
            <db_reference>
                <db_name>EMDB</db_name>
                <accession_id>EMD-0280</accession_id>
                <content_type>associated EM volume</content_type>
                <details>CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with bicuculline and megabody Mb38.</details>
            </db_reference>
        </other_db_list>
    </crossreferences>
    <sample>
        <name>Human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex with bicuculline and megabody Mb38.</name>
        <supramolecule_list>
            <complex_supramolecule supramolecule_id="1">
                <name>Human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex with bicuculline and megabody Mb38.</name>
                <parent>0</parent>
                <macromolecule_list>
                    <macromolecule>
                        <macromolecule_id>1</macromolecule_id>
                    </macromolecule>
                    <macromolecule>
                        <macromolecule_id>2</macromolecule_id>
                    </macromolecule>
                    <macromolecule>
                        <macromolecule_id>3</macromolecule_id>
                    </macromolecule>
                    <macromolecule>
                        <macromolecule_id>4</macromolecule_id>
                    </macromolecule>
                </macromolecule_list>
                <molecular_weight>
                    <theoretical units="MDa">0.33</theoretical>
                </molecular_weight>
            </complex_supramolecule>
            <complex_supramolecule supramolecule_id="2">
                <name>Human full-length heteromeric alpha1beta3gamma2L GABA(A)R</name>
                <parent>1</parent>
                <macromolecule_list>
                    <macromolecule>
                        <macromolecule_id>1</macromolecule_id>
                    </macromolecule>
                    <macromolecule>
                        <macromolecule_id>2</macromolecule_id>
                    </macromolecule>
                    <macromolecule>
                        <macromolecule_id>3</macromolecule_id>
                    </macromolecule>
                </macromolecule_list>
                <natural_source database="NCBI">
                    <organism ncbi="9606">Homo sapiens</organism>
                    <organ>Brain</organ>
                    <cellular_location>Plasma membrane</cellular_location>
                </natural_source>
            </complex_supramolecule>
            <complex_supramolecule supramolecule_id="3">
                <name>megabody Mb38</name>
                <parent>1</parent>
                <macromolecule_list>
                    <macromolecule>
                        <macromolecule_id>4</macromolecule_id>
                    </macromolecule>
                </macromolecule_list>
                <natural_source database="NCBI">
                    <organism ncbi="9844">Lama glama</organism>
                </natural_source>
            </complex_supramolecule>
        </supramolecule_list>
        <macromolecule_list>
            <protein_or_peptide macromolecule_id="1">
                <name>Gamma-aminobutyric acid receptor subunit alpha-1,Gamma-aminobutyric acid receptor subunit alpha-1</name>
                <natural_source database="NCBI">
                    <organism ncbi="9606">Homo sapiens</organism>
                </natural_source>
                <molecular_weight>
                    <theoretical units="MDa">0.05291660199999999</theoretical>
                </molecular_weight>
                <details>Potential signal peptide:
MKKSPGLSDY LWAWTLFLST LTGRSYG
FLAG tag:
DYKDDDDK,Potential signal peptide:
MKKSPGLSDY LWAWTLFLST LTGRSYG
FLAG tag:
DYKDDDDK</details>
                <number_of_copies>2</number_of_copies>
                <recombinant_expression database="NCBI">
                    <recombinant_organism ncbi="9606">Homo sapiens</recombinant_organism>
                </recombinant_expression>
                <enantiomer>LEVO</enantiomer>
                <sequence>
                    <string>MKKSPGLSDYLWAWTLFLSTLTGRSYGDYKDDDDKQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDI
FVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLRITEDG
TLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQS
STGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATA
MDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDPLIKKNNTYAPTATSYTPNLARGDPGLATIAKS
ATIEPKEVKPETKPPEPKKTFNSVSKIDRLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ</string>
                    <external_references type="UNIPROTKB">P08219</external_references>
                    <external_references type="UNIPROTKB">P14867</external_references>
                </sequence>
            </protein_or_peptide>
            <protein_or_peptide macromolecule_id="2">
                <name>Gamma-aminobutyric acid receptor subunit beta-3</name>
                <natural_source database="NCBI">
                    <organism ncbi="9606">Homo sapiens</organism>
                </natural_source>
                <molecular_weight>
                    <theoretical units="MDa">0.054444578</theoretical>
                </molecular_weight>
                <number_of_copies>2</number_of_copies>
                <recombinant_expression database="NCBI">
                    <recombinant_organism ncbi="9606">Homo sapiens</recombinant_organism>
                </recombinant_expression>
                <enantiomer>LEVO</enantiomer>
                <sequence>
                    <string>MCSGLLELLLPIWLSWTLGTRGSEPRSVNDPGNMSFVKETVDKLLKGYDIRLRPDFGGPPVCVGMNIDIASIDMVSEVNM
DYTLTMYFQQYWRDKRLAYSGIPLNLTLDNRVADQLWVPDTYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAA
CMMDLRRYPLDEQNCTLEIESYGYTTDDIEFYWRGGDKAVTGVERIELPQFSIVEHRLVSRNVVFATGAYPRLSLSFRLK
RNIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIPYVKAIDMYLMGCFVFVFLA
LLEYAFVNYIFFGRGPQRQKKLAEKTAKAKNDRSKSESNRVDAHGNILLTSLEVHNEMNEVSGGIGDTRNSAISFDNSGI
QYRKQSMPREGHGRFLGDRSLPHKKTHLRRRSSQLKIKIPDLTDVNAIDRWSRIVFPFTFSLFNLVYWLYYVN</string>
                    <external_references type="UNIPROTKB">P28472</external_references>
                </sequence>
            </protein_or_peptide>
            <protein_or_peptide macromolecule_id="3">
                <name>Gamma-aminobutyric acid receptor subunit gamma-2</name>
                <natural_source database="NCBI">
                    <organism ncbi="9606">Homo sapiens</organism>
                </natural_source>
                <molecular_weight>
                    <theoretical units="MDa">0.056922055</theoretical>
                </molecular_weight>
                <details>Linker sequence:
GGSGGSGGSGK
1D4 tag:
TETSQVAPA</details>
                <number_of_copies>1</number_of_copies>
                <recombinant_expression database="NCBI">
                    <recombinant_organism ncbi="9606">Homo sapiens</recombinant_organism>
                </recombinant_expression>
                <enantiomer>LEVO</enantiomer>
                <sequence>
                    <string>MSSPNIWSTGSSVYSTPVFSQKMTVWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTPKVPEGDVTVILNNLLEGYDNK
LRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWYDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADA
HWITTPNRMLRIWNDGRVLYTLRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQF
SFVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVPARTSLGITTVLTMTTLST
IARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSNRKPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMN
NATHLQERDEEYGYECLDGKDCASFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYLGGSGG
SGGSGKTETSQVAPA</string>
                    <external_references type="UNIPROTKB">P18507</external_references>
                </sequence>
            </protein_or_peptide>
            <protein_or_peptide macromolecule_id="4">
                <name>Megabody Mb38</name>
                <natural_source database="NCBI">
                    <organism ncbi="9844">Lama glama</organism>
                </natural_source>
                <molecular_weight>
                    <theoretical units="MDa">0.057784300999999996</theoretical>
                </molecular_weight>
                <details>6His tag:
HHHHHH
EPEA tag:
EPEA</details>
                <number_of_copies>1</number_of_copies>
                <recombinant_expression database="NCBI">
                    <recombinant_organism ncbi="562">Escherichia coli</recombinant_organism>
                </recombinant_expression>
                <enantiomer>LEVO</enantiomer>
                <sequence>
                    <string>QVQLQESGGGLVQTKTTTSVIDTTNDAQNLLTQAQTIVNTLKDYCPILIAKSSSSNGGTNNANTPSWQTAGGGKNSCATF
GAEFSAASDMINNAQKIVQETQQLSANQPKNITQPHNLNLNSPSSLTALAQKMLKNAQSQAEILKLANQVESDFNKLSSG
HLKDYIGKCDASAISSANMTMQNQKNNWGNGCAGVEETQSLLKTSAADFNNQTPQINQAQNLANTLIQELGNNPFRASGG
GSGGGGSGKLSDTYEQLSRLLTNDNGTNSKTSAQAINQAVNNLNERAKTLAGGTTNSPAYQATLLALRSVLGLWNSMGYA
VICGGYTKSPGENNQKDFHYTDENGNGTTINCGGSTNSNGTHSYNGTNTLKADKNVSLSIEQYEKIHEAYQILSKALKQA
GLAPLNSKGEKLEAHVTTSKYGSLRVSCAASGRTFTTYIMAWFRQAPGKEREFLAAMDQGRIQYYGDSVRGRFTISRDYA
KNSVDLQLDGLRPEDTAVYYCAAGAGFWGLRTASSYHYWGQGTQVTVSSHHHHHHEPEA</string>
                </sequence>
            </protein_or_peptide>
            <ligand macromolecule_id="9">
                <name>bicuculline methochloride</name>
                <molecular_weight>
                    <theoretical units="MDa">0.00036735199999999993</theoretical>
                </molecular_weight>
                <number_of_copies>2</number_of_copies>
                <formula>H0Z</formula>
            </ligand>
            <ligand macromolecule_id="10">
                <name>[(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate</name>
                <molecular_weight>
                    <theoretical units="MDa">0.000746566</theoretical>
                </molecular_weight>
                <number_of_copies>2</number_of_copies>
                <formula>PIO</formula>
            </ligand>
        </macromolecule_list>
    </sample>
    <structure_determination_list>
        <structure_determination structure_determination_id="1">
            <method>singleParticle</method>
            <aggregation_state>particle</aggregation_state>
            <specimen_preparation_list>
                <single_particle_preparation preparation_id="1">
                    <concentration units="mg/mL">0.1</concentration>
                    <buffer>
                        <ph>7.6</ph>
                    </buffer>
                    <grid>
                        <model>Quantifoil, UltrAuFoil, R1.2/1.3</model>
                        <material>GOLD</material>
                        <pretreatment>
                            <type>GLOW DISCHARGE</type>
                        </pretreatment>
                    </grid>
                    <vitrification>
                        <cryogen_name>ETHANE</cryogen_name>
                        <instrument>FEI VITROBOT MARK IV</instrument>
                    </vitrification>
                    <details>Monodisperse sample</details>
                </single_particle_preparation>
            </specimen_preparation_list>
            <microscopy_list>
                <single_particle_microscopy microscopy_id="1">
                    <microscope>FEI TITAN KRIOS</microscope>
                    <illumination_mode>FLOOD BEAM</illumination_mode>
                    <imaging_mode>BRIGHT FIELD</imaging_mode>
                    <electron_source>FIELD EMISSION GUN</electron_source>
                    <acceleration_voltage units="kV">300</acceleration_voltage>
                    <nominal_cs units="mm">2.7</nominal_cs>
                    <nominal_defocus_min units="µm">0.5</nominal_defocus_min>
                    <nominal_defocus_max units="µm">0.7000000000000001</nominal_defocus_max>
                    <nominal_magnification>75000.0</nominal_magnification>
                    <specimen_holder_model>FEI TITAN KRIOS AUTOGRID HOLDER</specimen_holder_model>
                    <cooling_holder_cryogen>NITROGEN</cooling_holder_cryogen>
                    <specialist_optics>
                        <phase_plate>VOLTA PHASE PLATE</phase_plate>
                    </specialist_optics>
                    <image_recording_list>
                        <image_recording image_recording_id="1">
                            <film_or_detector_model>FEI FALCON III (4k x 4k)</film_or_detector_model>
                            <detector_mode>COUNTING</detector_mode>
                            <average_electron_dose_per_image units="e/Å^2">30.0</average_electron_dose_per_image>
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