+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8hqc | ||||||
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タイトル | Structure of a GPCR-G protein in complex with a natural peptide agonist | ||||||
要素 |
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キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / G protein / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||
機能・相同性 | 機能・相同性情報 complement component C5a binding / cell proliferation in hindbrain / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / Peptide ligand-binding receptors / Regulation of Complement cascade / response to peptidoglycan / Terminal pathway of complement / membrane attack complex ...complement component C5a binding / cell proliferation in hindbrain / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / Peptide ligand-binding receptors / Regulation of Complement cascade / response to peptidoglycan / Terminal pathway of complement / membrane attack complex / G alpha (i) signalling events / mu-type opioid receptor binding / complement receptor mediated signaling pathway / Activation of C3 and C5 / corticotropin-releasing hormone receptor 1 binding / negative regulation of macrophage chemotaxis / vesicle docking involved in exocytosis / complement activation, alternative pathway / positive regulation of neutrophil chemotaxis / chemokine activity / endopeptidase inhibitor activity / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / positive regulation of macrophage chemotaxis / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / muscle contraction / positive regulation of chemokine production / complement activation, classical pathway / neutrophil chemotaxis / Neutrophil degranulation / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / positive regulation of epithelial cell proliferation / cognition / Regulation of Complement cascade / locomotory behavior / astrocyte activation / G protein-coupled receptor activity / microglial cell activation / mRNA transcription by RNA polymerase II / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / positive regulation of angiogenesis / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / chemotaxis / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / apical part of cell / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cell body / fibroblast proliferation / cytoplasmic vesicle / G alpha (s) signalling events / basolateral plasma membrane / G alpha (q) signalling events / killing of cells of another organism / negative regulation of neuron apoptotic process / Ras protein signal transduction 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) 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: 3.89 Å | ||||||
データ登録者 | Saha, S. / Maharana, J. / Yadav, M.K. / Sarma, P. / Chami, M. / Banerjee, R. / Shukla, A.K. | ||||||
資金援助 | インド, 1件
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引用 | ジャーナル: Cell / 年: 2023 タイトル: Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors. 著者: Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha ...著者: Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha Mishra / Htet A Khant / Mohamed Chami / Trent M Woodruff / Ramanuj Banerjee / Arun K Shukla / Cornelius Gati / 要旨: The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological ...The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders. #1: ジャーナル: Cell(Cambridge,Mass.) / 年: 2023 タイトル: Structure of a GPCR-G protein in complex with a synthetic peptide agonist 著者: Saha, S. / Maharana, J. / Yadav, M.K. / Sarma, P. / Chami, M. / Banerjee, R. / Shukla, A.K. | ||||||
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 | 8hqc.cif.gz | 213.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8hqc.ent.gz | 161.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8hqc.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 | 8hqc_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8hqc_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 8hqc_validation.xml.gz | 48.4 KB | 表示 | |
CIF形式データ | 8hqc_validation.cif.gz | 72.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/hq/8hqc ftp://data.pdbj.org/pub/pdb/validation_reports/hq/8hqc | HTTPS FTP |
-関連構造データ
関連構造データ | 34947MC 8hptC 8i95C 8i97C 8i9aC 8i9lC 8i9sC 8ia2C 8j6dC 8jzzC 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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-要素
-タンパク質 , 2種, 2分子 AD
#1: タンパク質 | 分子量: 44958.422 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: The initial sequence in the sample sequence is the expression tag (absent in the coordinates): "MGKTIIALSYIFCLVFADYKDDDDAANFTPVNGSSGNQSVRLVTSSSLEVLFQGPGSDPIDNSSFEINYDHYGTMDPNI" The residues ...詳細: The initial sequence in the sample sequence is the expression tag (absent in the coordinates): "MGKTIIALSYIFCLVFADYKDDDDAANFTPVNGSSGNQSVRLVTSSSLEVLFQGPGSDPIDNSSFEINYDHYGTMDPNI" The residues absent in the coordinates and present in the sample sequence belongs to disordered regions. 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: C5ar1, C5ar, C5r1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P30993 |
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#4: 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, CPAMD4 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P01031 |
-Guanine nucleotide-binding protein ... , 3種, 3分子 BCG
#2: タンパク質 | 分子量: 27024.762 Da / 分子数: 1 / Mutation: G42D,E43N,A227D,G230D,I332A,V335I / 由来タイプ: 組換発現 詳細: This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha called the "mini G(o) alpha";Expression tag: "MGHHHHHHENLYFQGT" Residues absent in the coordinates: Disordered ...詳細: This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha called the "mini G(o) alpha";Expression tag: "MGHHHHHHENLYFQGT" Residues absent in the coordinates: Disordered regions,This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha called the "mini G(o) alpha";Expression tag: "MGHHHHHHENLYFQGT" Residues absent in the coordinates: Disordered regions 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAO1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P09471 |
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#3: タンパク質 | 分子量: 38534.062 Da / 分子数: 1 / 由来タイプ: 組換発現 / 詳細: Expression tag: "MHHHHHHGSSGS" / 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 詳細: Residues absent in the coordinates: Disordered regions 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 |
-抗体 , 1種, 1分子 H
#6: 抗体 | 分子量: 27340.482 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: Residues absent in the coordinate file: Disordered regions 由来: (組換発現) Mus musculus (ハツカネズミ) / 発現宿主: Escherichia coli (大腸菌) |
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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 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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): 2500 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 42 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
画像スキャン | 動画フレーム数/画像: 40 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.89 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 173416 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||
拘束条件 |
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