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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8hnm | ||||||
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タイトル | CXCR3-DNGi complex activated by VUF11222 | ||||||
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![]() | SIGNALING PROTEIN / G protein coupled receptor / chemokine receptor / CXCR3 / VUF11222 / complex | ||||||
機能・相同性 | ![]() Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / regulation of leukocyte migration / C-X-C chemokine binding / chemokine binding / C-X-C chemokine receptor activity / chemokine receptor activity / positive regulation of chemotaxis / C-C chemokine receptor activity / negative regulation of execution phase of apoptosis ...Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / regulation of leukocyte migration / C-X-C chemokine binding / chemokine binding / C-X-C chemokine receptor activity / chemokine receptor activity / positive regulation of chemotaxis / C-C chemokine receptor activity / negative regulation of execution phase of apoptosis / C-C chemokine binding / Chemokine receptors bind chemokines / positive regulation of execution phase of apoptosis / negative regulation of endothelial cell proliferation / 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 / regulation of cell adhesion / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of angiogenesis / bioluminescence / cell chemotaxis / positive regulation of release of sequestered calcium ion into cytosol / Regulation of insulin secretion / G protein-coupled receptor binding / calcium-mediated signaling / electron transport chain / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / 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 / response to peptide hormone / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / positive regulation of angiogenesis / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / chemotaxis / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / signaling receptor activity / cell cortex / midbody / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / angiogenesis / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / cell surface receptor signaling pathway / cell adhesion / inflammatory response / iron ion binding / immune response / cell cycle 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() ![]() | ||||||
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: 2.94 Å | ||||||
![]() | Jiao, H.Z. / Hu, H.L. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into the activation and inhibition of CXC chemokine receptor 3. 著者: Haizhan Jiao / Bin Pang / Aijun Liu / Qiang Chen / Qi Pan / Xiankun Wang / Yunong Xu / Ying-Chih Chiang / Ruobing Ren / Hongli Hu / ![]() 要旨: The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in ...The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in type 1 immunity. Here we determined the structures of human CXCR3-DNG complexes activated by chemokine CXCL11, peptidomimetic agonist PS372424 and biaryl-type agonist VUF11222, and the structure of inactive CXCR3 bound to noncompetitive antagonist SCH546738. Structural analysis revealed that PS372424 shares a similar orthosteric binding pocket to the N terminus of CXCL11, while VUF11222 buries deeper and activates the receptor in a distinct manner. We showed an allosteric binding site between TM5 and TM6, accommodating SCH546738 in the inactive CXCR3. SCH546738 may restrain the receptor at an inactive state by preventing the repacking of TM5 and TM6. By revealing the binding patterns and the pharmacological properties of the four modulators, we present the activation mechanisms of CXCR3 and provide insights for future drug development. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 246.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 184.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 571.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 584.9 KB | 表示 | |
XML形式データ | ![]() | 23.3 KB | 表示 | |
CIF形式データ | ![]() | 35.8 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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 ABG
#1: タンパク質 | 分子量: 40445.059 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P63096 |
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#2: タンパク質 | 分子量: 42005.895 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P62873 |
#3: 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) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P59768 |
-タンパク質 / 抗体 , 2種, 2分子 RS
#4: タンパク質 | 分子量: 72918.008 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() ![]() 遺伝子: cybC, CXCR3, GPR9 発現宿主: ![]() ![]() 参照: UniProt: P0ABE7, UniProt: P49682, UniProt: Q9GV45, Oplophorus-luciferin 2-monooxygenase |
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#5: 抗体 | 分子量: 27784.896 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() |
-非ポリマー , 2種, 3分子 ![](data/chem/img/CLR.gif)
![](data/chem/img/4IE.gif)
![](data/chem/img/4IE.gif)
#6: 化合物 | #7: 化合物 | ChemComp-4IE / [ | |
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-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 | 名称: CXCR3-VUF11222-DNGi-scFv16 / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 濃度: 5 mg/ml / 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 / 湿度: 100 % |
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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 / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 1200 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm |
撮影 | 電子線照射量: 54.31 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
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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 | 名称: Gctf / カテゴリ: CTF補正 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.94 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 162856 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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