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万見- EMDB-37237: Cryo-EM structure of the GPR174-Gs complex bound to endogenous lysoPS -
+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-37237 | |||||||||
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タイトル | Cryo-EM structure of the GPR174-Gs complex bound to endogenous lysoPS | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR / Gs / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 bioactive lipid receptor activity / positive regulation of Rho protein signal transduction / negative regulation of interleukin-2 production / T cell homeostasis / PKA activation in glucagon signalling / hair follicle placode formation / centriolar satellite / developmental growth / D1 dopamine receptor binding / intracellular transport ...bioactive lipid receptor activity / positive regulation of Rho protein signal transduction / negative regulation of interleukin-2 production / T cell homeostasis / PKA activation in glucagon signalling / hair follicle placode formation / centriolar satellite / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / cognition / platelet aggregation / 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 / 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 / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.83 Å | |||||||||
データ登録者 | Nie Y / Qiu Z / Zheng S / Chen S | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive G signaling. 著者: Yingying Nie / Zeming Qiu / Sijia Chen / Zhao Chen / Xiaocui Song / Yan Ma / Niu Huang / Jason G Cyster / Sanduo Zheng / 要旨: Many orphan G protein-coupled receptors (GPCRs) remain understudied because their endogenous ligands are unknown. Here, we show that a group of class A/rhodopsin-like orphan GPCRs including GPR61, ...Many orphan G protein-coupled receptors (GPCRs) remain understudied because their endogenous ligands are unknown. Here, we show that a group of class A/rhodopsin-like orphan GPCRs including GPR61, GPR161 and GPR174 increase the cAMP level similarly to fully activated D1 dopamine receptor (D1R). We report cryo-electron microscopy structures of the GPR61‒G, GPR161‒G and GPR174‒G complexes without any exogenous ligands. The GPR174 structure reveals that endogenous lysophosphatidylserine (lysoPS) is copurified. While GPR174 fails to respond to exogenous lysoPS, likely owing to its maximal activation by the endogenous ligand, GPR174 mutants with lower ligand binding affinities can be specifically activated by lysoPS but not other lipids, in a dose-dependent manner. Moreover, GPR174 adopts a non-canonical G coupling mode. The structures of GPR161 and GPR61 reveal that the second extracellular loop (ECL2) penetrates into the orthosteric pocket, possibly contributing to constitutive activity. Our work definitively confirms lysoPS as an endogenous GPR174 ligand and suggests that high constitutive activity of some orphan GPCRs could be accounted for by their having naturally abundant ligands. | |||||||||
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_37237.map.gz | 20.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-37237-v30.xml emd-37237.xml | 21.7 KB 21.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_37237.png | 79.5 KB | ||
Filedesc metadata | emd-37237.cif.gz | 6.9 KB | ||
その他 | emd_37237_half_map_1.map.gz emd_37237_half_map_2.map.gz | 20.7 MB 20.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-37237 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37237 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_37237_validation.pdf.gz | 786.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_37237_full_validation.pdf.gz | 785.6 KB | 表示 | |
XML形式データ | emd_37237_validation.xml.gz | 10.3 KB | 表示 | |
CIF形式データ | emd_37237_validation.cif.gz | 12 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37237 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37237 | 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_37237.map.gz / 形式: CCP4 / 大きさ: 22.2 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: 1.08 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
-ハーフマップ: #2
ファイル | emd_37237_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: #1
ファイル | emd_37237_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 : Cryo-EM structure of the GPR174 and mini-Gs complex with Nb35
+超分子 #1: Cryo-EM structure of the GPR174 and mini-Gs complex with Nb35
+超分子 #2: GPR174
+超分子 #3: Gs complex
+超分子 #4: Nb35
+分子 #1: Probable G-protein coupled receptor 174
+分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #4: Nanobody 35
+分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #6: CHOLESTEROL
+分子 #7: O-{HYDROXY[((2R)-2-HYDROXY-3-{[(1S)-1-HYDROXYPENTADECYL]OXY}PROPY...
-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 | 7.0 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281 K / 装置: FEI VITROBOT MARK IV |
-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 BIOQUANTUM (6k x 4k) 実像数: 2943 / 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): 2.7800000000000002 µm 最小 デフォーカス(公称値): 1.3900000000000001 µm 倍率(公称値): 64000 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |