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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: 8hnn | ||||||
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タイトル | Structure of CXCR3 complexed with antagonist SCH546738 | ||||||
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![]() | SIGNALING PROTEIN / G protein coupled receptor / chemokine receptor / CXCR3 / SCH546738 / complex | ||||||
機能・相同性 | ![]() dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / regulation of leukocyte migration / sensory perception of temperature stimulus / positive regulation of eating behavior / C-X-C chemokine binding / adenylate cyclase-inhibiting opioid receptor signaling pathway / chemokine binding / G protein-coupled opioid receptor activity ...dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / regulation of leukocyte migration / sensory perception of temperature stimulus / positive regulation of eating behavior / C-X-C chemokine binding / adenylate cyclase-inhibiting opioid receptor signaling pathway / chemokine binding / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion / C-X-C chemokine receptor activity / G protein-coupled opioid receptor signaling pathway / chemokine receptor activity / positive regulation of dopamine secretion / sensory perception / positive regulation of potassium ion transmembrane transport / conditioned place preference / positive regulation of chemotaxis / C-C chemokine receptor activity / maternal behavior / negative regulation of execution phase of apoptosis / C-C chemokine binding / receptor serine/threonine kinase binding / neuropeptide binding / Chemokine receptors bind chemokines / positive regulation of p38MAPK cascade / eating behavior / positive regulation of execution phase of apoptosis / negative regulation of endothelial cell proliferation / behavioral response to cocaine / estrous cycle / neuropeptide signaling pathway / regulation of cell adhesion / MECP2 regulates neuronal receptors and channels / axon terminus / sensory perception of pain / T-tubule / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of angiogenesis / Peptide ligand-binding receptors / cell chemotaxis / positive regulation of release of sequestered calcium ion into cytosol / sarcoplasmic reticulum / locomotory behavior / calcium-mediated signaling / cellular response to glucose stimulus / electron transport chain / response to nicotine / response to insulin / adenylate cyclase-activating G protein-coupled receptor signaling pathway / synaptic vesicle membrane / response to estrogen / positive regulation of angiogenesis / chemotaxis / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / signaling receptor activity / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / chemical synaptic transmission / cellular response to lipopolysaccharide / postsynaptic membrane / perikaryon / angiogenesis / response to ethanol / defense response to virus / periplasmic space / electron transfer activity / cell surface receptor signaling pathway / cell adhesion / inflammatory response / neuron projection / iron ion binding / immune response / G protein-coupled receptor signaling pathway / external side of plasma membrane / apoptotic process / dendrite / heme binding / positive regulation of cell population proliferation / cell surface / positive regulation of transcription by RNA polymerase II / mitochondrion / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol 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: 3.6 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 | ![]() | 89.4 KB | 表示 | ![]() |
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PDB形式 | ![]() | 61.1 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 | ![]() | 496.2 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 499.4 KB | 表示 | |
XML形式データ | ![]() | 9.5 KB | 表示 | |
CIF形式データ | ![]() | 13.9 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
#1: 抗体 | 分子量: 18665.906 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 発現宿主: ![]() ![]() |
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#2: タンパク質 | 分子量: 56327.051 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, OPRK1, OPRK 発現宿主: ![]() ![]() 参照: UniProt: P0ABE7, UniProt: P49682, UniProt: P41145 |
#3: 化合物 | ChemComp-43I / |
#4: 化合物 | ChemComp-CLR / |
研究の焦点であるリガンドがあるか | Y |
-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-KOR-SCH546738-Nb6 / タイプ: COMPLEX / Entity ID: #1-#2 / 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): 2000 nm / 最小 デフォーカス(公称値): 1500 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm |
撮影 | 電子線照射量: 53.43 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
EMソフトウェア | 名称: Gctf / カテゴリ: CTF補正 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 509297 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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