登録情報 データベース : PDB / ID : 6dw0 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the benzodiazepine-sensitive alpha1beta1gamma2S tri-heteromeric GABAA receptor in complex with GABA (Whole map) 要素(Gamma-aminobutyric acid receptor subunit ...) x 3 詳細 キーワード MEMBRANE PROTEIN (膜タンパク質) / Neurotransmission / GABA Receptors / GABA / Cys Loop Receptors / Ion Channel (イオンチャネル)機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
GABA receptor activation / diazepam binding / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / chemical synaptic transmission, postsynaptic / monoatomic anion channel activity / benzodiazepine receptor activity / inhibitory synapse / GABA receptor complex / organic cyclic compound binding / inhibitory extracellular ligand-gated monoatomic ion channel activity ... GABA receptor activation / diazepam binding / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / chemical synaptic transmission, postsynaptic / monoatomic anion channel activity / benzodiazepine receptor activity / inhibitory synapse / GABA receptor complex / organic cyclic compound binding / inhibitory extracellular ligand-gated monoatomic ion channel activity / cellular response to histamine / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly / GABA receptor binding / neurotransmitter receptor activity / synaptic transmission, GABAergic / postsynaptic specialization membrane / gamma-aminobutyric acid signaling pathway / 月経周期 / chloride transport / adult behavior / chloride channel activity / central nervous system neuron development / transmembrane transporter complex / chloride channel complex / ligand-gated monoatomic ion channel activity / GABA-ergic synapse / regulation of postsynaptic membrane potential / monoatomic ion transport / presynaptic active zone membrane / monoatomic ion transmembrane transport / chloride transmembrane transport / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / post-embryonic development / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / response to progesterone / Schaffer collateral - CA1 synapse / cytoplasmic vesicle membrane / response to toxic substance / 核膜 / postsynapse / chemical synaptic transmission / receptor complex / neuron projection / 神経繊維 / glutamatergic synapse / シナプス / 樹状突起 / 細胞膜 類似検索 - 分子機能 Gamma-aminobutyric-acid A receptor, gamma 2 subunit / Gamma-aminobutyric acid receptor subunit gamma-1/4 / : / Gamma-aminobutyric-acid A receptor, alpha 1 subunit / Gamma-aminobutyric-acid A receptor, beta subunit / : / Gamma-aminobutyric-acid A receptor, alpha subunit / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. ... Gamma-aminobutyric-acid A receptor, gamma 2 subunit / Gamma-aminobutyric acid receptor subunit gamma-1/4 / : / Gamma-aminobutyric-acid A receptor, alpha 1 subunit / Gamma-aminobutyric-acid A receptor, beta subunit / : / Gamma-aminobutyric-acid A receptor, alpha subunit / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / 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 類似検索 - ドメイン・相同性 GAMMA-AMINO-BUTANOIC ACID / Gamma-aminobutyric acid receptor subunit beta-1 / Gamma-aminobutyric acid receptor subunit gamma-2 / Gamma-aminobutyric acid receptor subunit alpha-1 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.8 Å 詳細データ登録者 Phulera, S. / Zhu, H. / Yu, J. / Yoshioka, C. / Gouaux, E. 資金援助 米国, 2件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01 GM100400 米国 Howard Hughes Medical Institute (HHMI) 米国
引用ジャーナル : Elife / 年 : 2018タイトル : Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABA receptor in complex with GABA.著者 : Swastik Phulera / Hongtao Zhu / Jie Yu / Derek P Claxton / Nate Yoder / Craig Yoshioka / Eric Gouaux / 要旨 : Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABA ... Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABA receptors implicated in multiple neurological diseases. Despite the profound importance of heteromeric GABA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of a tri-heteromeric α1β1γ2S GABA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABA receptors and a framework for rational design of novel therapeutic agents. 履歴 登録 2018年6月26日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2018年8月8日 Provider : repository / タイプ : Initial release改定 1.1 2019年11月20日 Group : Author supporting evidence / カテゴリ : pdbx_audit_support / Item : _pdbx_audit_support.funding_organization改定 2.0 2020年7月29日 Group : Atomic model / Data collection ... Atomic model / Data collection / Derived calculations / Structure summary カテゴリ : atom_site / chem_comp ... atom_site / chem_comp / em_entity_assembly / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn / struct_site / struct_site_gen Item : _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ... _atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _chem_comp.type / _em_entity_assembly.entity_id_list / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id 解説 : Carbohydrate remediation / Provider : repository / タイプ : Remediation改定 3.0 2023年11月15日 Group : Atomic model / Data collection ... Atomic model / Data collection / Database references / Derived calculations / Structure summary カテゴリ : atom_site / chem_comp ... atom_site / chem_comp / chem_comp_atom / chem_comp_bond / database_2 / struct_conn Item : _atom_site.auth_atom_id / _atom_site.label_atom_id ... _atom_site.auth_atom_id / _atom_site.label_atom_id / _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag
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