登録情報 データベース : PDB / ID : 7pc0 構造の表示 ダウンロードとリンクタイトル GABA-A receptor bound by a-Cobratoxin 要素(Gamma-aminobutyric acid receptor subunit alpha- ...) x 2 Alpha-cobratoxin Gamma-aminobutyric acid receptor subunit beta-3 Megabody 25 詳細キーワード MEMBRANE PROTEIN / neurotransmission / toxin / GABA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
circadian sleep/wake cycle, REM sleep / reproductive behavior / acetylcholine receptor inhibitor activity / GABA receptor complex / hard palate development / cellular response to histamine / ion channel regulator activity / GABA receptor activation / inner ear receptor cell development / inhibitory synapse assembly ... circadian sleep/wake cycle, REM sleep / reproductive behavior / acetylcholine receptor inhibitor activity / GABA receptor complex / hard palate development / cellular response to histamine / ion channel regulator activity / GABA receptor activation / inner ear receptor cell development / inhibitory synapse assembly / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / innervation / response to anesthetic / postsynaptic specialization membrane / inhibitory postsynaptic potential / gamma-aminobutyric acid signaling pathway / synaptic transmission, GABAergic / cellular response to zinc ion / exploration behavior / motor behavior / roof of mouth development / Signaling by ERBB4 / cochlea development / social behavior / chloride channel complex / dendrite membrane / cytoplasmic vesicle membrane / chloride transmembrane transport / cerebellum development / learning / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / GABA-ergic synapse / memory / toxin activity / dendritic spine / postsynaptic membrane / postsynapse / response to xenobiotic stimulus / cell surface / signal transduction / extracellular region / identical protein binding / plasma membrane 類似検索 - 分子機能 Snake toxin, conserved site / Snake toxins signature. / : / Snake toxin cobra-type / Snake three-finger toxin / Gamma-aminobutyric-acid A receptor, alpha 1 subunit / : / Gamma-aminobutyric-acid A receptor, alpha subunit / : / Gamma-aminobutyric-acid A receptor, beta subunit ... Snake toxin, conserved site / Snake toxins signature. / : / Snake toxin cobra-type / Snake three-finger toxin / Gamma-aminobutyric-acid A receptor, alpha 1 subunit / : / Gamma-aminobutyric-acid A receptor, alpha subunit / : / Gamma-aminobutyric-acid A receptor, beta subunit / Snake toxin-like superfamily / 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 HEXANE / HISTAMINE / Alpha-cobratoxin / Gamma-aminobutyric acid receptor subunit alpha-1 / Gamma-aminobutyric acid receptor subunit beta-3 類似検索 - 構成要素生物種 Lama glama (ラマ)Homo sapiens (ヒト)Naja kaouthia (コブラ)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 Å 詳細データ登録者 Kasaragod, V.B. / Miller, P.S. 資金援助 英国, 1件 詳細 詳細を隠す組織 認可番号 国 Wellcome Trust 英国
引用ジャーナル : Nature / 年 : 2022タイトル : Mechanisms of inhibition and activation of extrasynaptic αβ GABA receptors.著者 : Vikram Babu Kasaragod / Martin Mortensen / Steven W Hardwick / Ayla A Wahid / Valentina Dorovykh / Dimitri Y Chirgadze / Trevor G Smart / Paul S Miller / 要旨 : Type A GABA (γ-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of α-, β-, γ-, δ-, ε-, ρ-, θ- and π-subunits. αβ, ... Type A GABA (γ-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of α-, β-, γ-, δ-, ε-, ρ-, θ- and π-subunits. αβ, α4βδ, α6βδ and α5βγ receptors favour extrasynaptic localization, and mediate an essential persistent (tonic) inhibitory conductance in many regions of the mammalian brain. Mutations of these receptors in humans are linked to epilepsy and insomnia. Altered extrasynaptic receptor function is implicated in insomnia, stroke and Angelman and Fragile X syndromes, and drugs targeting these receptors are used to treat postpartum depression. Tonic GABAergic responses are moderated to avoid excessive suppression of neuronal communication, and can exhibit high sensitivity to Zn blockade, in contrast to synapse-preferring α1βγ, α2βγ and α3βγ receptor responses. Here, to resolve these distinctive features, we determined structures of the predominantly extrasynaptic αβ GABA receptor class. An inhibited state bound by both the lethal paralysing agent α-cobratoxin and Zn was used in comparisons with GABA-Zn and GABA-bound structures. Zn nullifies the GABA response by non-competitively plugging the extracellular end of the pore to block chloride conductance. In the absence of Zn, the GABA signalling response initially follows the canonical route until it reaches the pore. In contrast to synaptic GABA receptors, expansion of the midway pore activation gate is limited and it remains closed, reflecting the intrinsic low efficacy that characterizes the extrasynaptic receptor. Overall, this study explains distinct traits adopted by αβ receptors that adapt them to a role in tonic signalling. 履歴 登録 2021年8月3日 登録サイト : PDBE / 処理サイト : PDBE改定 1.0 2022年2月9日 Provider : repository / タイプ : Initial release改定 2.0 2022年2月16日 Group : Advisory / Atomic model ... Advisory / Atomic model / Data collection / Database references / Derived calculations / Polymer sequence / Source and taxonomy / Structure summary カテゴリ : atom_site / atom_site_anisotrop ... atom_site / atom_site_anisotrop / em_entity_assembly / entity / entity_name_com / entity_poly / entity_poly_seq / entity_src_gen / entity_src_nat / pdbx_branch_scheme / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_poly_seq_scheme / pdbx_struct_conn_angle / pdbx_struct_sheet_hbond / pdbx_unobs_or_zero_occ_residues / pdbx_validate_close_contact / pdbx_validate_polymer_linkage / pdbx_validate_torsion / struct_asym / struct_conf / struct_conn / struct_mon_prot_cis / struct_ref / struct_ref_seq / struct_ref_seq_dif / struct_sheet_range Item : _atom_site_anisotrop.pdbx_auth_seq_id / _atom_site_anisotrop.pdbx_label_seq_id ... _atom_site_anisotrop.pdbx_auth_seq_id / _atom_site_anisotrop.pdbx_label_seq_id / _em_entity_assembly.entity_id_list / _entity_name_com.entity_id / _entity_name_com.name / _pdbx_branch_scheme.entity_id / _pdbx_entity_branch.entity_id / _pdbx_entity_branch_descriptor.entity_id / _pdbx_entity_branch_link.entity_id / _pdbx_entity_branch_list.entity_id / _pdbx_entity_nonpoly.entity_id / _pdbx_nonpoly_scheme.entity_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_sheet_hbond.range_1_auth_seq_id / _pdbx_struct_sheet_hbond.range_1_label_seq_id / _pdbx_struct_sheet_hbond.range_2_auth_seq_id / _pdbx_struct_sheet_hbond.range_2_label_seq_id / _pdbx_validate_close_contact.auth_seq_id_2 / _pdbx_validate_torsion.auth_seq_id / _struct_asym.entity_id / _struct_conf.beg_auth_seq_id / _struct_conf.beg_label_seq_id / _struct_conf.end_auth_seq_id / _struct_conf.end_label_seq_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_seq_id / _struct_mon_prot_cis.label_seq_id / _struct_mon_prot_cis.pdbx_label_seq_id_2 / _struct_ref.db_code / _struct_ref.db_name / _struct_ref.entity_id / _struct_ref.pdbx_align_begin / _struct_ref.pdbx_db_accession / _struct_ref.pdbx_seq_one_letter_code / _struct_sheet_range.beg_auth_seq_id / _struct_sheet_range.beg_label_seq_id / _struct_sheet_range.end_auth_seq_id / _struct_sheet_range.end_label_seq_id 改定 2.1 2022年2月23日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID改定 2.2 2022年3月2日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first / _citation.page_last改定 2.3 2024年11月13日 Group : Data collection / Structure summaryカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature Item : _em_admin.last_update / _pdbx_entry_details.has_protein_modification
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