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データを開く
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基本情報
| 登録情報 | ![]() | ||||||||||||
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| タイトル | Structure of mouse C5a-desArg bound mouse C5aR1 in complex with Go | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | GPCR / G protein / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
| 機能・相同性 | 機能・相同性情報Terminal pathway of complement / Activation of C3 and C5 / presynapse organization / Peptide ligand-binding receptors / complement component C5a receptor activity / Regulation of Complement cascade / membrane attack complex / response to peptidoglycan / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity ...Terminal pathway of complement / Activation of C3 and C5 / presynapse organization / Peptide ligand-binding receptors / complement component C5a receptor activity / Regulation of Complement cascade / membrane attack complex / response to peptidoglycan / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / G alpha (i) signalling events / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement activation, alternative pathway / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / endopeptidase inhibitor activity / G protein-coupled dopamine receptor signaling pathway / regulation of locomotion / positive regulation of macrophage chemotaxis / regulation of heart contraction / parallel fiber to Purkinje cell synapse / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / complement activation, classical pathway / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / postsynaptic modulation of chemical synaptic transmission / neutrophil chemotaxis / Neutrophil degranulation / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / astrocyte activation / muscle contraction / positive regulation of epithelial cell proliferation / locomotory behavior / mRNA transcription by RNA polymerase II / microglial cell activation / negative regulation of insulin secretion / G protein-coupled receptor activity / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / cognition / G-protein beta/gamma-subunit complex binding / 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 / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of angiogenesis / apical part of cell / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / presynaptic membrane / cell body / GTPase binding / Ca2+ pathway / cytoplasmic vesicle / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / basolateral plasma membrane / G alpha (q) signalling events / killing of cells of another organism 類似検索 - 分子機能 | ||||||||||||
| 生物種 | ![]() Homo sapiens (ヒト) | ||||||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.13 Å | ||||||||||||
データ登録者 | Banerjee R / Yadav MK / Yadav R / Ganguly M / Mishra S / Dalal A / Gati C / Shukla AK | ||||||||||||
| 資金援助 | インド, 英国, 3件
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引用 | ジャーナル: bioRxiv / 年: 2025タイトル: Molecular fingerprints of a convergent mechanism orchestrating diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptors. 著者: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / Cedric ...著者: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / Cedric S Cui / Xaria X Li / John D Lee / Calvin Aaron Dsouza / Shirsha Saha / Parishmita Sarma / Ganita Rawat / Houming Zhu / Htet A Khant / Richard J Clark / Fumiya K Sano / Ramanuj Banerjee / Trent M Woodruff / Osamu Nureki / Cornelius Gati / Arun K Shukla / ![]() 要旨: Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and ...Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and orchestrating inflammatory responses. They continue to be important therapeutic targets for multiple disorders including autoimmune diseases, acute and chronic inflammation, and allergy-related conditions. Recent structural coverage has provided important insights into their activation and signaling, however, confounding observations in the literature related to ligand efficacy and functional responses, especially in different model systems, present a major challenge for drug discovery efforts. Here, we systematically and comprehensively profile a broad set of natural and synthetic ligands at C3aR and C5aR1 and discover a previously unanticipated level of functional specialization in terms of species-specific pharmacology and receptor activation. Taking a lead from this, we determine seventeen cryo-EM structures of different ligand-receptor-G-protein complexes and uncover distinct orientation of agonists between the human and mouse receptors despite an overlapping positioning in the orthosteric binding pocket. Combined with extensive mutagenesis and functional assays, these structural snapshots allow us to decode and validate a convergent molecular mechanism involving a "Five-Point-Switch" in these receptors that orchestrates the recognition and efficacy of diverse agonists. We also identify species-specific differences at the level of phosphorylation patterns encoded in the carboxyl-terminus of these receptors and directly visualize their impact on βarr binding and activation using cryo-EM structures. Interestingly, we observe that βarrs engage with the mouse C5aR1 using a variation of previously discovered P-X-P-P phosphorylation motif via a "Sliding-Mechanism" and also exhibit distinct oligomeric state for the human vs. mouse receptors. Taken together, this study elucidates functional specialization at the complement anaphylatoxin receptors and underlying molecular mechanisms, offering a previously lacking framework with direct and immediate implications for the development of novel therapeutics. | ||||||||||||
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構造の表示
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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_62619.map.gz | 57.5 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-62619-v30.xml emd-62619.xml | 27.2 KB 27.2 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_62619_fsc.xml | 8.4 KB | 表示 | FSCデータファイル |
| 画像 | emd_62619.png | 68.9 KB | ||
| Filedesc metadata | emd-62619.cif.gz | 7.3 KB | ||
| その他 | emd_62619_half_map_1.map.gz emd_62619_half_map_2.map.gz | 59.5 MB 59.5 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-62619 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-62619 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_62619_validation.pdf.gz | 730.5 KB | 表示 | EMDB検証レポート |
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| 文書・詳細版 | emd_62619_full_validation.pdf.gz | 730.1 KB | 表示 | |
| XML形式データ | emd_62619_validation.xml.gz | 16 KB | 表示 | |
| CIF形式データ | emd_62619_validation.cif.gz | 20.6 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-62619 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-62619 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9kwxMC ![]() 9kugC ![]() 9kutC ![]() 9kv6C ![]() 9kv8C ![]() 9kvpC ![]() 9kwgC ![]() 9kx6C ![]() 9kxsC ![]() 9ky2C ![]() 9kyuC ![]() 9kz2C ![]() 9kz8C ![]() 9kzkC ![]() 9l0hC ![]() 9umjC ![]() 9umrC ![]() 9umxC 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 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_62619.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 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: 1.294 Å | ||||||||||||||||||||||||||||||||||||
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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_62619_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_62619_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 |
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試料の構成要素
+全体 : mouse C5a-desArg bound to mouse C5aR1 in complex with Go
+超分子 #1: mouse C5a-desArg bound to mouse C5aR1 in complex with Go
+超分子 #2: mouse C5a anaphylatoxin chemotactic receptor 1
+超分子 #3: Guanine nucleotide-binding protein G(o) subunit alpha
+超分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+超分子 #5: mouse C5a-desArg anaphylatoxin
+超分子 #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+超分子 #7: Antibody fragment ScFv16
+分子 #1: Muscarinic acetylcholine receptor M4,C5a anaphylatoxin chemotacti...
+分子 #2: Guanine nucleotide-binding protein G(o) subunit alpha
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: Antibody fragment ScFv16
+分子 #6: C5a anaphylatoxin
-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 |
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試料調製
| 緩衝液 | pH: 7.4 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 検出モード: COUNTING / 平均電子線量: 40.0 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): 3.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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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 |
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| 得られたモデル | ![]() PDB-9kwx: |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
インド,
英国, 3件
引用







































































Z (Sec.)
Y (Row.)
X (Col.)






































FIELD EMISSION GUN


