+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30974 | |||||||||
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タイトル | Serotonin 1D (5-HT1D) receptor-Gi protein complex | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 intestine smooth muscle contraction / adenylate cyclase-inhibiting serotonin receptor signaling pathway / regulation of behavior / Serotonin receptors / serotonin binding / vasoconstriction / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / regulation of locomotion / plasma membrane => GO:0005886 ...intestine smooth muscle contraction / adenylate cyclase-inhibiting serotonin receptor signaling pathway / regulation of behavior / Serotonin receptors / serotonin binding / vasoconstriction / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / regulation of locomotion / plasma membrane => GO:0005886 / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / electron transport chain / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / chemical synaptic transmission / Extra-nuclear estrogen signaling / cell population proliferation / periplasmic space / electron transfer activity / iron ion binding / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / dendrite / heme binding / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
データ登録者 | Xu P / Huang S / Zhang H / Mao C / Zhou XE / Shen DD / Jiang Y / Zhang Y / Xu HE | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nature / 年: 2021 タイトル: Structural insights into the lipid and ligand regulation of serotonin receptors. 著者: Peiyu Xu / Sijie Huang / Huibing Zhang / Chunyou Mao / X Edward Zhou / Xi Cheng / Icaro A Simon / Dan-Dan Shen / Hsin-Yung Yen / Carol V Robinson / Kasper Harpsøe / Bo Svensson / Jia Guo / ...著者: Peiyu Xu / Sijie Huang / Huibing Zhang / Chunyou Mao / X Edward Zhou / Xi Cheng / Icaro A Simon / Dan-Dan Shen / Hsin-Yung Yen / Carol V Robinson / Kasper Harpsøe / Bo Svensson / Jia Guo / Hualiang Jiang / David E Gloriam / Karsten Melcher / Yi Jiang / Yan Zhang / H Eric Xu / 要旨: Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter that activates the largest subtype family of G-protein-coupled receptors. Drugs that target 5-HT, 5-HT, 5-HT and other 5-HT ...Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter that activates the largest subtype family of G-protein-coupled receptors. Drugs that target 5-HT, 5-HT, 5-HT and other 5-HT receptors are used to treat numerous disorders. 5-HT receptors have high levels of basal activity and are subject to regulation by lipids, but the structural basis for the lipid regulation and basal activation of these receptors and the pan-agonism of 5-HT remains unclear. Here we report five structures of 5-HT receptor-G-protein complexes: 5-HT in the apo state, bound to 5-HT or bound to the antipsychotic drug aripiprazole; 5-HT bound to 5-HT; and 5-HT in complex with a 5-HT- and 5-HT-selective agonist, BRL-54443. Notably, the phospholipid phosphatidylinositol 4-phosphate is present at the G-protein-5-HT interface, and is able to increase 5-HT-mediated G-protein activity. The receptor transmembrane domain is surrounded by cholesterol molecules-particularly in the case of 5-HT, in which cholesterol molecules are directly involved in shaping the ligand-binding pocket that determines the specificity for aripiprazol. Within the ligand-binding pocket of apo-5-HT are structured water molecules that mimic 5-HT to activate the receptor. Together, our results address a long-standing question of how lipids and water molecules regulate G-protein-coupled receptors, reveal how 5-HT acts as a pan-agonist, and identify the determinants of drug recognition in 5-HT receptors. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_30974.map.gz | 17.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30974-v30.xml emd-30974.xml | 18.2 KB 18.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30974.png | 48.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30974 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30974 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30974_validation.pdf.gz | 372.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30974_full_validation.pdf.gz | 371.9 KB | 表示 | |
XML形式データ | emd_30974_validation.xml.gz | 5.7 KB | 表示 | |
CIF形式データ | emd_30974_validation.cif.gz | 6.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30974 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30974 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_30974.map.gz / 形式: CCP4 / 大きさ: 27 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
+全体 : Serotonin 1D (5-HT1D) receptor-Gi protein complex
+超分子 #1: Serotonin 1D (5-HT1D) receptor-Gi protein complex
+超分子 #2: receptor-Gi protein
+超分子 #3: scFv16
+分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: scFv16
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: Soluble cytochrome b562,5-hydroxytryptamine receptor 1D
+分子 #6: SEROTONIN
+分子 #7: CHOLESTEROL
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 検出モード: COUNTING / 平均電子線量: 70.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 倍率(補正後): 47847 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
粒子像選択 | 選択した数: 1486169 |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 141501 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |