+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7t6u | ||||||
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タイトル | Structure of the human FPR2-Gi complex with CGEN-855A | ||||||
要素 |
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キーワード | SIGNALING PROTEIN / GPCR / membrane protein | ||||||
機能・相同性 | 機能・相同性情報 N-formyl peptide receptor activity / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / complement receptor mediated signaling pathway / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste ...N-formyl peptide receptor activity / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / complement receptor mediated signaling pathway / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of innate immune response / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / Formyl peptide receptors bind formyl peptides and many other ligands / ADP signalling through P2Y purinoceptor 12 / positive regulation of monocyte chemotaxis / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cargo receptor activity / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / positive chemotaxis / tertiary granule membrane / ficolin-1-rich granule membrane / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / specific granule membrane / positive regulation of superoxide anion generation / positive regulation of phagocytosis / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / astrocyte activation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / receptor-mediated endocytosis / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / microglial cell activation / negative regulation of inflammatory response / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to amyloid-beta / cellular response to prostaglandin E stimulus / GPER1 signaling / GDP binding / chemotaxis / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Rattus (ネズミ) Bos taurus (ウシ) Homo (哺乳類) | ||||||
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: 2.9 Å | ||||||
データ登録者 | Zhuang, Y.W. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2. 著者: Youwen Zhuang / Lei Wang / Jia Guo / Dapeng Sun / Yue Wang / Weiyi Liu / H Eric Xu / Cheng Zhang / 要旨: The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally ...The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of G-coupled FPR1 and FPR2 bound to a formylpeptide and G-coupled FPR2 bound to two synthetic peptide and small-molecule agonists. Together with mutagenesis data, our structures reveal the molecular mechanism of formylpeptide recognition by FPRs and structural variations of FPR1 and FPR2 leading to their different ligand preferences. Structural analysis also suggests that diverse FPR agonists sample a conserved activation chamber at the bottom of ligand-binding pockets to activate FPRs. Our results provide a basis for rational drug design on FPRs. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7t6u.cif.gz | 212.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7t6u.ent.gz | 166.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7t6u.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7t6u_validation.pdf.gz | 773.2 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7t6u_full_validation.pdf.gz | 778.2 KB | 表示 | |
XML形式データ | 7t6u_validation.xml.gz | 35.2 KB | 表示 | |
CIF形式データ | 7t6u_validation.cif.gz | 54.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/t6/7t6u ftp://data.pdbj.org/pub/pdb/validation_reports/t6/7t6u | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABC
#1: タンパク質 | 分子量: 40313.863 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI1 / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P63096 |
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#2: タンパク質 | 分子量: 39021.648 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus (ネズミ) / 遺伝子: Gnb1 / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P54311 |
#3: タンパク質 | 分子量: 7432.554 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P63212 |
-抗体 / タンパク質・ペプチド / タンパク質 / 非ポリマー , 4種, 5分子 ELR
#4: 抗体 | 分子量: 26323.324 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus (ネズミ) / 遺伝子: Igh-V7183, Gm16592 / 発現宿主: Spodoptera (蝶・蛾) |
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#5: タンパク質・ペプチド | 分子量: 1074.275 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo (哺乳類) |
#6: タンパク質 | 分子量: 43246.332 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: FPR2, FPRH1, FPRL1, LXA4R / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P25090 |
#7: 化合物 |
-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 |
-試料調製
構成要素 | 名称: formylpeptide receptors FPR2 WITH FMLFII / タイプ: COMPLEX / Entity ID: #1-#6 / 由来: MULTIPLE SOURCES | ||||||||||||||||
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由来(天然) |
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由来(組換発現) | 生物種: Spodoptera (蝶・蛾) | ||||||||||||||||
緩衝液 | pH: 7.2 | ||||||||||||||||
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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 5000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 70 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.14_3260: / 分類: 精密化 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 594109 / 対称性のタイプ: POINT |