+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-34943 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Structure of C5a-pep bound mouse C5aR1 in complex with Go | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | GPCR / G protein / SIGNALING PROTEIN / SIGNATLING 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 / G alpha (i) signalling events / mu-type opioid receptor binding ...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 / G alpha (i) signalling events / mu-type opioid receptor binding / complement receptor mediated signaling pathway / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / 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 / neutrophil chemotaxis / Neutrophil degranulation / G-protein beta/gamma-subunit complex binding / positive regulation of epithelial cell proliferation / cognition / 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 / 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 / negative regulation of neuron apoptotic process / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / defense response to Gram-positive bacterium / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / dendrite / synapse / GTP binding / protein-containing complex binding / cell surface 類似検索 - 分子機能 | |||||||||
生物種 | Mus musculus (ハツカネズミ) / Homo sapiens (ヒト) / synthetic construct (人工物) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.39 Å | |||||||||
データ登録者 | Saha S / Maharana J / Yadav MK / Sarma P / Chami M / Banerjee R / Shukla AK | |||||||||
資金援助 | インド, 1件
| |||||||||
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 MK / Sarma P / Chami M / Banerjee R / Shukla AK | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_34943.map.gz | 168 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-34943-v30.xml emd-34943.xml | 26.7 KB 26.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_34943_fsc.xml | 11.9 KB | 表示 | FSCデータファイル |
画像 | emd_34943.png | 33.2 KB | ||
Filedesc metadata | emd-34943.cif.gz | 7.4 KB | ||
その他 | emd_34943_half_map_1.map.gz emd_34943_half_map_2.map.gz | 165 MB 165 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-34943 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34943 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_34943_validation.pdf.gz | 846.3 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_34943_full_validation.pdf.gz | 845.9 KB | 表示 | |
XML形式データ | emd_34943_validation.xml.gz | 20.6 KB | 表示 | |
CIF形式データ | emd_34943_validation.cif.gz | 26.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34943 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34943 | HTTPS FTP |
-関連構造データ
関連構造データ | 8hptMC 8hqcC 8i95C 8i97C 8i9aC 8i9lC 8i9sC 8ia2C 8j6dC 8jzzC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_34943.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.94756 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-ハーフマップ: #2
ファイル | emd_34943_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_34943_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
+全体 : GPCR-G protein in complex with a synthetic peptide agonist
+超分子 #1: GPCR-G protein in complex with a synthetic peptide agonist
+超分子 #2: C5a anaphylatoxin chemotactic receptor 1
+超分子 #3: synthetic peptide
+超分子 #4: Guanine nucleotide-binding protein G(o) subunit alpha
+超分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+超分子 #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+超分子 #7: Antibody fragment
+分子 #1: C5a anaphylatoxin chemotactic receptor 1
+分子 #2: MEA-LYS-PRO-ZAL-ALC-DAR
+分子 #3: Guanine nucleotide-binding protein G(o) subunit alpha
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #6: Antibody fragment ScFv16
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
---|---|
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 42.0 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 |
+画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
---|---|
得られたモデル | PDB-8hpt: |