+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8g05 | ||||||||||||
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タイトル | Cryo-EM structure of an orphan GPCR-Gi protein signaling complex | ||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / GPCR / agonist / 6-OAU | ||||||||||||
機能・相同性 | 機能・相同性情報 urotensin II receptor activity / tertiary granule membrane / neuropeptide signaling pathway / 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 / specific granule membrane / regulation of mitotic spindle organization ...urotensin II receptor activity / tertiary granule membrane / neuropeptide signaling pathway / 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 / specific granule membrane / 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 / 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 / Extra-nuclear estrogen signaling / receptor complex / cell population proliferation / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / Neutrophil degranulation / 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) | ||||||||||||
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 | ||||||||||||
データ登録者 | Zhang, X. / Wang, Y.J. / Li, X. / Liu, G.B. / Gong, W.M. / Zhang, C. | ||||||||||||
資金援助 | 米国, 中国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Pro-phagocytic function and structural basis of GPR84 signaling. 著者: Xuan Zhang / Yujing Wang / Shreyas Supekar / Xu Cao / Jingkai Zhou / Jessica Dang / Siqi Chen / Laura Jenkins / Sara Marsango / Xiu Li / Guibing Liu / Graeme Milligan / Mingye Feng / Hao Fan ...著者: Xuan Zhang / Yujing Wang / Shreyas Supekar / Xu Cao / Jingkai Zhou / Jessica Dang / Siqi Chen / Laura Jenkins / Sara Marsango / Xiu Li / Guibing Liu / Graeme Milligan / Mingye Feng / Hao Fan / Weimin Gong / Cheng Zhang / 要旨: GPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely pro-inflammatory, which can augment ...GPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely pro-inflammatory, which can augment inflammatory response, and GPR84 also functions as a pro-phagocytic receptor to enhance phagocytic activities of macrophages. In this study, we show that the activation of GPR84 by the synthetic agonist 6-OAU can synergize with the blockade of CD47 on cancer cells to induce phagocytosis of cancer cells by macrophages. We also determine a high-resolution structure of the GPR84-G signaling complex with 6-OAU. This structure reveals an occluded binding pocket for 6-OAU, the molecular basis of receptor activation involving non-conserved structural motifs of GPR84, and an unusual G-coupling interface. Together with computational docking and simulations studies, this structure also suggests a mechanism for the high selectivity of GPR84 for MCFAs and a potential routes of ligand binding and dissociation. These results provide a framework for understanding GPR84 signaling and developing new drugs targeting GPR84. | ||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8g05.cif.gz | 220.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8g05.ent.gz | 168.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8g05.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8g05_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8g05_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 8g05_validation.xml.gz | 39.1 KB | 表示 | |
CIF形式データ | 8g05_validation.cif.gz | 59.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/g0/8g05 ftp://data.pdbj.org/pub/pdb/validation_reports/g0/8g05 | HTTPS FTP |
-関連構造データ
関連構造データ | 29645MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#2: タンパク質 | 分子量: 40414.047 Da / 分子数: 1 / Mutation: S47N, G203A, E245A, A326S / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63096 |
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#3: タンパク質 | 分子量: 40845.559 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#5: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
-タンパク質 / 抗体 , 2種, 2分子 RE
#1: タンパク質 | 分子量: 48699.938 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GPR84, EX33 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q9NQS5 |
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#4: 抗体 | 分子量: 28694.805 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) |
-非ポリマー , 2種, 2分子
#6: 化合物 | ChemComp-YI9 / |
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#7: 化合物 | ChemComp-CLR / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: 6OAU_GPR84_DNGi_scFv16 / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
由来(組換発現) | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 55 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.14_3260: / 分類: 精密化 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 62864 / 対称性のタイプ: POINT |