+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8hk5 | ||||||
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タイトル | C5aR1-Gi-C5a protein complex | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / GPCR (Gタンパク質共役受容体) / C5aR1 / C5a / complement | ||||||
機能・相同性 | 機能・相同性情報 complement component C5a signaling pathway / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / response to peptidoglycan / Terminal pathway of complement / 膜侵襲複合体 / sensory perception of chemical stimulus / complement receptor mediated signaling pathway / Activation of C3 and C5 ...complement component C5a signaling pathway / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / response to peptidoglycan / Terminal pathway of complement / 膜侵襲複合体 / sensory perception of chemical stimulus / complement receptor mediated signaling pathway / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / 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 / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / positive regulation of neutrophil chemotaxis / G alpha (i) signalling events / complement activation, alternative pathway / Thrombin signalling through proteinase activated receptors (PARs) / alkylglycerophosphoethanolamine phosphodiesterase activity / chemokine activity / photoreceptor outer segment membrane / spectrin binding / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / amyloid-beta clearance / activation of phospholipase C activity / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / positive regulation of vascular endothelial growth factor production / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / cellular defense response / complement activation, classical pathway / regulation of mitotic spindle organization / positive regulation of chemokine production / cellular response to forskolin / cardiac muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Peptide ligand-binding receptors / 好中球 / secretory granule membrane / Regulation of insulin secretion / positive regulation of epithelial cell proliferation / G protein-coupled receptor activity / Regulation of Complement cascade / G protein-coupled receptor binding / astrocyte activation / microglial cell activation / G-protein beta/gamma-subunit complex binding / mRNA transcription by RNA polymerase II / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / 認識 / G alpha (z) signalling events / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / GDP binding / positive regulation of angiogenesis / heterotrimeric G-protein complex / 走化性 / signaling receptor complex adaptor activity / retina development in camera-type eye / apical part of cell / GTPase binding / cell body / phospholipase C-activating G protein-coupled receptor signaling pathway / 細胞皮質 / midbody / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / G alpha (s) signalling events / basolateral plasma membrane / killing of cells of another organism / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Rattus norvegicus (ドブネズミ) Bos taurus (ウシ) | ||||||
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 | Wang, Y. / Liu, W. / Xu, Y. / Zhuang, Y. / Xu, H.E. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Chem Biol / 年: 2023 タイトル: Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. 著者: Yue Wang / Weiyi Liu / Youwei Xu / Xinheng He / Qingning Yuan / Ping Luo / Wenjia Fan / Jingpeng Zhu / Xinyue Zhang / Xi Cheng / Yi Jiang / H Eric Xu / Youwen Zhuang / 要旨: The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations ...The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders. | ||||||
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 | 8hk5.cif.gz | 184.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8hk5.ent.gz | 141.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8hk5.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/hk/8hk5 ftp://data.pdbj.org/pub/pdb/validation_reports/hk/8hk5 | HTTPS FTP |
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-関連構造データ
関連構造データ | 34846MC 8hk2C 8hk3C 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
-タンパク質 , 2種, 2分子 AB
#1: タンパク質 | 分子量: 39372.375 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: C5AR1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P21730 |
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#2: タンパク質 | 分子量: 8288.676 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: C5 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P01031 |
-Guanine nucleotide-binding protein ... , 3種, 3分子 CDG
#3: タンパク質 | 分子量: 40313.863 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: GNAI1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63096 |
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#4: タンパク質 | 分子量: 37915.496 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Gnb1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P54311 |
#5: タンパク質 | 分子量: 7432.554 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: A0A6J0WY55 |
-非ポリマー , 1種, 2分子
#6: 化合物 |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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: C5aR1-Gi-C5a protein complex / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: MULTIPLE SOURCES |
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分子量 | 値: 0.16 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.2 |
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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 5000 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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粒子像の選択 | 選択した粒子像数: 4236350 |
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: 406559 / 対称性のタイプ: POINT |