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基本情報
登録情報 | データベース: PDB / ID: 8hpt | ||||||
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タイトル | Structure of C5a-pep bound mouse C5aR1 in complex with Go | ||||||
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![]() | SIGNATLING PROTEIN/IMMUNE SYSTEM / GPCR / G protein / SIGNALING PROTEIN / SIGNATLING PROTEIN-IMMUNE SYSTEM complex | ||||||
機能・相同性 | ![]() 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 / positive regulation of epithelial cell proliferation / astrocyte activation / neutrophil chemotaxis / Neutrophil degranulation / mRNA transcription by RNA polymerase II / locomotory behavior / G protein-coupled receptor activity / microglial cell activation / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / positive regulation of angiogenesis / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / 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 / basolateral plasma membrane / G alpha (i) signalling events / cell body / fibroblast proliferation / cytoplasmic vesicle / G alpha (s) signalling events / Ras protein signal transduction / G alpha (q) signalling events / negative regulation of neuron apoptotic process / Extra-nuclear estrogen signaling / cell population proliferation / 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 / synapse / dendrite / protein-containing complex binding / GTP binding / cell surface 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() synthetic construct (人工物) | ||||||
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: 3.39 Å | ||||||
![]() | Saha, S. / Maharana, J. / Yadav, M.K. / Sarma, P. / Chami, M. / Banerjee, R. / Shukla, A.K. | ||||||
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. #1: ![]() 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. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 221.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 165.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 47.8 KB | 表示 | |
CIF形式データ | ![]() | 70.8 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 | ![]() 34943MC ![]() 8hqcC ![]() 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 ( |
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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
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集合体
登録構造単位 | ![]()
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要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 BCG
#3: 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 (Uniprot ID: P09471) called the "mini G(o) alpha";The initial sequence in the provided sample sequence is the ...詳細: This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha (Uniprot ID: P09471) called the "mini G(o) alpha";The initial sequence in the provided sample sequence is the expression tag: "MGHHHHHHENLYFQGT",This is a variant of Guanine nucleotide-binding protein G(o) subunit alpha (Uniprot ID: P09471) called the "mini G(o) alpha";The initial sequence in the provided sample sequence is the expression tag: "MGHHHHHHENLYFQGT" 由来: (組換発現) ![]() ![]() ![]() |
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#4: タンパク質 | 分子量: 37198.656 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: The initial sequence present in the sample sequence and absent in the coordinates is the expression tag: "MHHHHHHGSSGS" 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P62873 |
#5: タンパク質 | 分子量: 6160.126 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: The missing residues in the coordinates are the regions which are disordered. 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P59768 |
-タンパク質 / タンパク質・ペプチド / 抗体 , 3種, 3分子 ADH
#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): "MGKTIIALSYIFCLVFADYKDDDDAANFTPVNGSSGNQSVRLVTSSSLEVLFQGPGSDPIDNSSFEINYDHYGTMDPNIPADGIHLPKRQP" ...詳細: The initial sequence in the sample sequence is the expression tag (absent in the coordinates): "MGKTIIALSYIFCLVFADYKDDDDAANFTPVNGSSGNQSVRLVTSSSLEVLFQGPGSDPIDNSSFEINYDHYGTMDPNIPADGIHLPKRQP" The residues missing in the coordinates as compared to the sample sequence are the residues with disorder. 由来: (組換発現) ![]() ![]() 発現宿主: ![]() ![]() 参照: UniProt: P30993 |
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#2: タンパク質・ペプチド | 分子量: 869.148 Da / 分子数: 1 / 由来タイプ: 合成 詳細: This is a chemically synthesized peptide derived from the C-terminus of human C5a. 由来: (合成) synthetic construct (人工物) |
#6: 抗体 | 分子量: 27340.482 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: The residues absent in the coordinates are the regions which are disordered. 由来: (組換発現) ![]() ![]() ![]() ![]() |
-詳細
研究の焦点であるリガンドがあるか | Y |
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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 |
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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 |
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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: ![]() |
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 |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / 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: 3.39 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 380463 / 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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