+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32018 | |||||||||
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タイトル | cryo-EM structure of LTB4-bound BLT1 in complex with Gi protein | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 leukotriene B4 receptor activity / leukotriene receptor activity / Leukotriene receptors / G protein-coupled peptide receptor activity / neuropeptide signaling pathway / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling ...leukotriene B4 receptor activity / leukotriene receptor activity / Leukotriene receptors / G protein-coupled peptide receptor activity / neuropeptide signaling pathway / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / muscle contraction / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / adenylate cyclase-modulating G protein-coupled receptor 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 / Prostacyclin signalling through prostacyclin receptor / response to peptide hormone / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / GDP binding / 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) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / 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 / cell population proliferation / Extra-nuclear estrogen signaling / inflammatory response / immune response / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / GTPase activity / nucleotide binding / centrosome / synapse / protein-containing complex binding / GTP binding / nucleolus / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol / cytoplasm 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: 2.9 Å | |||||||||
データ登録者 | He Y / Wang N | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Structural basis of leukotriene B4 receptor 1 activation. 著者: Na Wang / Xinheng He / Jing Zhao / Hualiang Jiang / Xi Cheng / Yu Xia / H Eric Xu / Yuanzheng He / 要旨: Leukotriene B4 receptor 1 (BLT1) plays crucial roles in the acute inflammatory responses and is a valuable target for anti-inflammation treatment, however, the mechanism by which leukotriene B4 (LTB4) ...Leukotriene B4 receptor 1 (BLT1) plays crucial roles in the acute inflammatory responses and is a valuable target for anti-inflammation treatment, however, the mechanism by which leukotriene B4 (LTB4) activates receptor remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structure of the LTB4 -bound human BLT1 in complex with a G protein in an active conformation at resolution of 2.91 Å. In combination of molecule dynamics (MD) simulation, docking and site-directed mutagenesis, our structure reveals that a hydrogen-bond network of water molecules and key polar residues is the key molecular determinant for LTB4 binding. We also find that the displacement of residues M101 and I271 to the center of receptor, which unlock the ion lock of the lower part of pocket, is the key mechanism of receptor activation. In addition, we reveal a binding site of phosphatidylinositol (PI) and discover that the widely open ligand binding pocket may contribute the lack of specificity and efficacy for current BLT1-targeting drug design. Taken together, our structural analysis provides a scaffold for understanding BLT1 activation and a rational basis for designing anti-leukotriene drugs. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
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_32018.map.gz | 59.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32018-v30.xml emd-32018.xml | 16.4 KB 16.4 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_32018_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_32018.png | 80.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32018 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32018 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_32018_validation.pdf.gz | 465.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_32018_full_validation.pdf.gz | 465.4 KB | 表示 | |
XML形式データ | emd_32018_validation.xml.gz | 11 KB | 表示 | |
CIF形式データ | emd_32018_validation.cif.gz | 14.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32018 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32018 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「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_32018.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
+全体 : BLT1/Gi complex
+超分子 #1: BLT1/Gi complex
+分子 #1: Leukotriene B4 receptor 1
+分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+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: scFv16
+分子 #6: LEUKOTRIENE B4
+分子 #7: CHOLESTEROL HEMISUCCINATE
+分子 #8: [(2R)-2-[(Z)-hexadec-9-enoyl]oxy-3-[oxidanyl-[(2S,3R,5R,6S)-2,3,4...
+分子 #9: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | 3D array |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 60.0 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: OTHER / 撮影モード: BRIGHT FIELD 最大 デフォーカス(公称値): 2.3000000000000003 µm 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |