+
データを開く
-
基本情報
| 登録情報 | ![]() | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | Structure of mouse C5a-desArg 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 / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
| 機能・相同性 | 機能・相同性情報Terminal pathway of complement / C5a anaphylatoxin chemotactic receptor binding / Activation of C3 and C5 / complement component C5a binding / cell proliferation in hindbrain / presynapse organization / complement component C5a signaling pathway / negative regulation of norepinephrine secretion / negative regulation of dopamine secretion / Regulation of Complement cascade ...Terminal pathway of complement / C5a anaphylatoxin chemotactic receptor binding / Activation of C3 and C5 / complement component C5a binding / cell proliferation in hindbrain / presynapse organization / complement component C5a signaling pathway / negative regulation of norepinephrine secretion / negative regulation of dopamine secretion / Regulation of Complement cascade / complement component C5a receptor activity / membrane attack complex / Peptide ligand-binding receptors / response to peptidoglycan / complement activation, lectin pathway / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / leukocyte migration involved in inflammatory response / inflammatory response to wounding / G alpha (i) signalling events / complement activation, GZMK pathway / negative regulation of macrophage chemotaxis / neutrophil homeostasis / glomerulus development / other organism cell membrane / positive regulation of chemotaxis / mu-type opioid receptor binding / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / vesicle docking involved in exocytosis / corticotropin-releasing hormone receptor 1 binding / transmembrane transporter complex / complement receptor mediated signaling pathway / complement activation, alternative pathway / leukocyte chemotaxis / complement activation / positive regulation of neutrophil chemotaxis / chemokine activity / G protein-coupled dopamine receptor signaling pathway / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / regulation of locomotion / regulation of heart contraction / parallel fiber to Purkinje cell synapse / amyloid-beta clearance / complement activation, classical pathway / positive regulation of vascular endothelial growth factor production / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / postsynaptic modulation of chemical synaptic transmission / positive regulation of chemokine production / neutrophil chemotaxis / Neutrophil degranulation / astrocyte activation / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / muscle contraction / positive regulation of epithelial cell proliferation / kidney development / locomotory behavior / microglial cell activation / negative regulation of insulin secretion / mRNA transcription by RNA polymerase II / G protein-coupled receptor activity / GABA-ergic synapse / cognition / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / chemotaxis / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / intracellular calcium ion homeostasis / apical part of cell / positive regulation of angiogenesis / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / 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 / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling 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
| ||||||||||||
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. | ||||||||||||
| 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_62619.map.gz | 57.5 MB | EMDBマップデータ形式 | |
|---|---|---|---|---|
| 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 |
-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 ( |
|---|---|
| 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_62619.map.gz / 形式: CCP4 / 大きさ: 64 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: 1.294 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_62619_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_62619_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 : 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 |
|---|---|
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 | TFS KRIOS |
|---|---|
| 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 |
+
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-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


