+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7wvx | ||||||||||||
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タイトル | Cryo-EM structure of the human formyl peptide receptor 2 in complex with fhumanin and Gi2 | ||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN / G protein-coupled receptor / formyl peptide receptor / FPR2 / humanin | ||||||||||||
機能・相同性 | 機能・相同性情報 negative regulation of interleukin-18 production / N-formyl peptide receptor activity / complement receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / immune response-regulating cell surface receptor signaling pathway / receptor antagonist activity / scavenger receptor binding / negative regulation of neuroinflammatory response / negative regulation of interleukin-1 production / G protein-coupled adenosine receptor signaling pathway ...negative regulation of interleukin-18 production / N-formyl peptide receptor activity / complement receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / immune response-regulating cell surface receptor signaling pathway / receptor antagonist activity / scavenger receptor binding / negative regulation of neuroinflammatory response / negative regulation of interleukin-1 production / G protein-coupled adenosine receptor signaling pathway / negative regulation of NLRP3 inflammasome complex assembly / negative regulation of calcium ion-dependent exocytosis / complement receptor mediated signaling pathway / positive regulation of urine volume / negative regulation of adenylate cyclase activity / negative regulation of execution phase of apoptosis / positive regulation of neural precursor cell proliferation / positive regulation of innate immune response / negative regulation of amyloid fibril formation / positive regulation of monocyte chemotaxis / Formyl peptide receptors bind formyl peptides and many other ligands / leukocyte chemotaxis / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / negative regulation of response to oxidative stress / cargo receptor activity / positive chemotaxis / neuronal dense core vesicle / tertiary granule membrane / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / ficolin-1-rich granule membrane / sperm flagellum / Adenylate cyclase inhibitory pathway / specific granule membrane / positive regulation of insulin receptor signaling pathway / positive regulation of phagocytosis / supramolecular fiber organization / positive regulation of vascular associated smooth muscle cell proliferation / sperm midpiece / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / receptor-mediated endocytosis / G-protein beta/gamma-subunit complex binding / response to nutrient / positive regulation of superoxide anion generation / mitochondrion organization / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / calcium-mediated signaling / electron transport chain / microglial cell activation / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of inflammatory response / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to amyloid-beta / chemotaxis / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling / GTPase binding / retina development in camera-type eye / signaling receptor activity / Ca2+ pathway 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||
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: 2.8 Å | ||||||||||||
データ登録者 | Zhu, Y. / Lin, X. / Zong, X. / Han, S. / Zhao, Q. / Wu, B. | ||||||||||||
資金援助 | 中国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Structural basis of FPR2 in recognition of Aβ and neuroprotection by humanin. 著者: Ya Zhu / Xiaowen Lin / Xin Zong / Shuo Han / Mu Wang / Yuxuan Su / Limin Ma / Xiaojing Chu / Cuiying Yi / Qiang Zhao / Beili Wu / 要旨: Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage ...Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage by Aβ, implying its involvement in the pathogenesis of Alzheimer's disease (AD). However, the interaction pattern between FPR2 and Aβ or humanin remains unknown. Here we report the structures of FPR2 bound to G and Aβ or N-formyl humanin (fHN). Combined with functional data, the structures reveal two critical regions that govern recognition and activity of Aβ and fHN, including a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. In addition, the structures of FPR2 and FPR1 in complex with different formyl peptides were determined, providing insights into ligand recognition and selectivity of the FPR family. These findings uncover key factors that define the functionality of FPR2 in AD and other inflammatory diseases and would enable drug development. | ||||||||||||
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 | 7wvx.cif.gz | 179.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7wvx.ent.gz | 135.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7wvx.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 | 7wvx_validation.pdf.gz | 809.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7wvx_full_validation.pdf.gz | 818.1 KB | 表示 | |
XML形式データ | 7wvx_validation.xml.gz | 30.3 KB | 表示 | |
CIF形式データ | 7wvx_validation.cif.gz | 44.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/wv/7wvx ftp://data.pdbj.org/pub/pdb/validation_reports/wv/7wvx | HTTPS FTP |
-関連構造データ
関連構造データ | 32861MC 7wvuC 7wvvC 7wvwC 7wvyC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質・ペプチド | 分子量: 2719.275 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: Q8IVG9 |
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#2: タンパク質 | 分子量: 56710.328 Da / 分子数: 1 / Mutation: S211L / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: cybC, FPR2, FPRH1, FPRL1, LXA4R 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P0ABE7, UniProt: P25090 |
#3: タンパク質 | 分子量: 40502.863 Da / 分子数: 1 / Mutation: S47N, G204A, A327S, E246A / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI2, GNAI2B 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P04899 |
#4: タンパク質 | 分子量: 38744.371 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: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#5: タンパク質 | 分子量: 7861.143 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: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
研究の焦点であるリガンドがあるか | N |
-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: Formyl peptide receptor 2 in complex with fhumanin and Gi2 タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.5 |
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: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 2.1875 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
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: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1398841 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 52.75 Å2 | ||||||||||||||||||||||||
拘束条件 |
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