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基本情報
登録情報 | ![]() | |||||||||||||||
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タイトル | Structure of EP141-C3aR-Go complex | |||||||||||||||
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![]() | GPCR / SIGNALING PROTEIN | |||||||||||||||
機能・相同性 | ![]() complement component C3a receptor activity / complement component C5a receptor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / blood circulation / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway ...complement component C3a receptor activity / complement component C5a receptor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / blood circulation / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / positive regulation of macrophage chemotaxis / positive regulation of vascular endothelial growth factor production / postsynaptic modulation of chemical synaptic transmission / Purinergic signaling in leishmaniasis infection / specific granule membrane / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / Peptide ligand-binding receptors / Regulation of Complement cascade / locomotory behavior / calcium-mediated signaling / negative regulation of insulin secretion / G protein-coupled receptor activity / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / positive regulation of angiogenesis / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / chemotaxis / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / 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 / cell body / positive regulation of cytosolic calcium ion concentration / presynaptic membrane / GTPase binding / Ca2+ pathway / 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 / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (q) signalling events / Ras protein signal transduction / postsynaptic membrane / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / inflammatory response / lysosomal membrane / GTPase activity / dendrite / synapse / Neutrophil degranulation / GTP binding / protein-containing complex binding / glutamatergic synapse / signal transduction / extracellular exosome 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() ![]() ![]() | |||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | |||||||||||||||
![]() | Yadav MK / Yadav R / Maharana J / Sarma P / Banerjee R / Shukla AK / Gati C | |||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() 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. | |||||||||||||||
履歴 |
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構造の表示
添付画像 |
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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 | ![]() | 85.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.7 KB 21.7 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.5 KB | 表示 | ![]() |
画像 | ![]() | 104.1 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
その他 | ![]() ![]() | 84.6 MB 84.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 825.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 825.4 KB | 表示 | |
XML形式データ | ![]() | 17.2 KB | 表示 | |
CIF形式データ | ![]() | 22.1 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8j6dMC ![]() 8hptC ![]() 8hqcC ![]() 8i95C ![]() 8i97C ![]() 8i9aC ![]() 8i9lC ![]() 8i9sC ![]() 8ia2C ![]() 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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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 | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 1.15 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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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: #1
ファイル | emd_36001_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: #2
ファイル | emd_36001_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 : Structure of EP141-C3aR-Go complex
全体 | 名称: Structure of EP141-C3aR-Go complex |
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要素 |
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-超分子 #1: Structure of EP141-C3aR-Go complex
超分子 | 名称: Structure of EP141-C3aR-Go complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
-分子 #1: Guanine nucleotide-binding protein G(o) subunit alpha
分子 | 名称: Guanine nucleotide-binding protein G(o) subunit alpha タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 28.193939 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYDQ VLHEDETTNR MHESLMLFDS ICNNKFFIDT S IILFLNKK ...文字列: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYDQ VLHEDETTNR MHESLMLFDS ICNNKFFIDT S IILFLNKK DLFGEKIKKS PLTICFPEYT GPNTYEDAAA YIQAQFESKN RSPNKEIYCH MTCATDTNNA QVIFDAVTDI II ANNLRGC GLY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(o) subunit alpha |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 38.534062 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: C3a anaphylatoxin chemotactic receptor
分子 | 名称: C3a anaphylatoxin chemotactic receptor / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 59.808422 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSASF SAETNSTDLL SQPWNEPPVI LSMVILSLT FLLGLPGNGL VLWVAGLKMQ RTVNTIWFLH LTLADLLCCL SLPFSLAHLA LQGQWPYGRF LCKLIPSIIV L NMFASVFL ...文字列: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSASF SAETNSTDLL SQPWNEPPVI LSMVILSLT FLLGLPGNGL VLWVAGLKMQ RTVNTIWFLH LTLADLLCCL SLPFSLAHLA LQGQWPYGRF LCKLIPSIIV L NMFASVFL LTAISLDRCL VVFKPIWCQN HRNVGMACSI CGCIWVVAFV MCIPVFVYRE IFTTDNHNRC GYKFGLSSSL DY PDFYGDP LENRSLENIV QPPGEMNDRL DPSSFQTNDH PWTVPTVFQP QTFQRPSADS LPRGSARLTS QNLYSNVFKP ADV VSPKIP SGFPIEDHET SPLDNSDAFL STHLKLFPSA SSNSFYESEL PQGFQDYYNL GQFTDDDQVP TPLVAITITR LVVG FLLPS VIMIACYSFI VFRMQRGRFA KSQSKTFRVA VVVVAVFLVC WTPYHIFGVL SLLTDPETPL GKTLMSWDHV CIALA SANS CFNPFLYALL GKDFRKKARQ SIQGILEAAF SEELTRSTHC PSNNVISERN STTV UniProtKB: C3a anaphylatoxin chemotactic receptor |
-分子 #4: EP141 peptide agonist
分子 | 名称: EP141 peptide agonist / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 1.825188 KDa |
配列 | 文字列: WWGKKYRASK LGLAR |
-分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #6: Antibody fragment - ScFv16
分子 | 名称: Antibody fragment - ScFv16 / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 26.466486 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL K |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 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 GLACIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: ![]() |
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 |
試料ステージ | ホルダー冷却材: NITROGEN |