[日本語] English
万見- EMDB-34097: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556 -
+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-34097 | |||||||||
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タイトル | Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556 | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Lysosphingolipid and LPA receptors / : / lysophosphatidic acid binding / negative regulation of cilium assembly / regulation of synaptic vesicle cycle / corpus callosum development / bleb assembly ...cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Lysosphingolipid and LPA receptors / : / lysophosphatidic acid binding / negative regulation of cilium assembly / regulation of synaptic vesicle cycle / corpus callosum development / bleb assembly / oligodendrocyte development / negative regulation of cAMP-mediated signaling / cellular response to oxygen levels / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / regulation of metabolic process / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / regulation of postsynaptic neurotransmitter receptor internalization / G alpha (q) signalling events / : / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / optic nerve development / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of Rho protein signal transduction / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of dendritic spine development / photoreceptor outer segment / G-protein alpha-subunit binding / GABA-ergic synapse / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / neurogenesis / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / positive regulation of stress fiber assembly / myelination / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / cerebellum development / cell chemotaxis / dendritic shaft / Regulation of insulin secretion / G protein-coupled receptor binding / PDZ domain binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) / Homo sapiens (ヒト) / Bos taurus (ウシ) / 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: 3.5 Å | |||||||||
データ登録者 | Akasaka H / Shihoya W / Nureki O | |||||||||
資金援助 | 日本, 1件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Structure of the active G-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist. 著者: Hiroaki Akasaka / Tatsuki Tanaka / Fumiya K Sano / Yuma Matsuzaki / Wataru Shihoya / Osamu Nureki / 要旨: Lysophosphatidic acid receptor 1 (LPA) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA is a drug target for various diseases, ...Lysophosphatidic acid receptor 1 (LPA) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA is a drug target for various diseases, including cancer, inflammation, and neuropathic pain. Notably, LPA agonists have potential therapeutic value for obesity and urinary incontinence. Here, we report a cryo-electron microscopy structure of the active human LPA-G complex bound to ONO-0740556, an LPA analog with more potent activity against LPA. Our structure elucidated the details of the agonist binding mode and receptor activation mechanism mediated by rearrangements of transmembrane segment 7 and the central hydrophobic core. A structural comparison of LPA and other phylogenetically-related lipid-sensing GPCRs identified the structural determinants for lipid preference of LPA. Moreover, we characterized the structural polymorphisms at the receptor-G-protein interface, which potentially reflect the G-protein dissociation process. Our study provides insights into the detailed mechanism of LPA binding to agonists and paves the way toward the design of drug-like agonists targeting LPA. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_34097.map.gz | 7.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-34097-v30.xml emd-34097.xml | 23 KB 23 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_34097_fsc.xml | 8.9 KB | 表示 | FSCデータファイル |
画像 | emd_34097.png | 29.5 KB | ||
マスクデータ | emd_34097_msk_1.map | 8 MB | マスクマップ | |
その他 | emd_34097_half_map_1.map.gz emd_34097_half_map_2.map.gz | 7.5 MB 7.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-34097 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34097 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_34097_validation.pdf.gz | 655.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_34097_full_validation.pdf.gz | 655.4 KB | 表示 | |
XML形式データ | emd_34097_validation.xml.gz | 11.1 KB | 表示 | |
CIF形式データ | emd_34097_validation.cif.gz | 15.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34097 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34097 | 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_34097.map.gz / 形式: CCP4 / 大きさ: 8 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: 1.1952 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_34097_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_34097_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_34097_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556
+超分子 #1: Human Lysophosphatidic Acid Receptor 1-Gi complex bound to ONO-0740556
+超分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+超分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
+超分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+超分子 #5: Lysophosphatidic Acid Receptor 1
+超分子 #6: scFv16
+分子 #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: Lysophosphatidic acid receptor 1
+分子 #5: scFv16
+分子 #6: [(2~{R})-2-[5-(2-hexylphenyl)pentanoylamino]-3-oxidanyl-propyl] d...
-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
濃度 | 7 mg/mL |
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緩衝液 | pH: 8 |
凍結 | 凍結剤: ETHANE |
-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) / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |