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基本情報
登録情報 | データベース: PDB / ID: 7xa3 | |||||||||||||||||||||
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タイトル | Cryo-EM structure of the CCL2 bound CCR2-Gi complex | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / GPCR / CCR2 / Chemokine Receptor / MEMBRNE PROTEIN | |||||||||||||||||||||
機能・相同性 | ![]() T-helper 17 cell chemotaxis / chemokine (C-C motif) ligand 2 binding / chemokine (C-C motif) ligand 12 binding / negative regulation of eosinophil degranulation / positive regulation of immune complex clearance by monocytes and macrophages / positive regulation of CD8-positive, alpha-beta T cell extravasation / positive regulation of astrocyte chemotaxis / leukocyte adhesion to vascular endothelial cell / chemokine (C-C motif) ligand 7 binding / helper T cell extravasation ...T-helper 17 cell chemotaxis / chemokine (C-C motif) ligand 2 binding / chemokine (C-C motif) ligand 12 binding / negative regulation of eosinophil degranulation / positive regulation of immune complex clearance by monocytes and macrophages / positive regulation of CD8-positive, alpha-beta T cell extravasation / positive regulation of astrocyte chemotaxis / leukocyte adhesion to vascular endothelial cell / chemokine (C-C motif) ligand 7 binding / helper T cell extravasation / chemokine (C-C motif) ligand 2 signaling pathway / positive regulation of thymocyte migration / positive regulation of hematopoietic stem cell migration / positive regulation of NMDA glutamate receptor activity / monocyte extravasation / CCR2 chemokine receptor binding / regulation of vascular endothelial growth factor production / negative regulation of natural killer cell chemotaxis / negative regulation of type 2 immune response / Beta defensins / positive regulation of monocyte extravasation / regulation of macrophage migration / macrophage migration / neutrophil clearance / regulation of T cell cytokine production / astrocyte cell migration / positive regulation of leukocyte tethering or rolling / chemokine receptor activity / negative regulation of glial cell apoptotic process / positive regulation of T-helper 1 type immune response / positive regulation of T cell chemotaxis / inflammatory response to wounding / CCR chemokine receptor binding / positive regulation of apoptotic cell clearance / ATF4 activates genes in response to endoplasmic reticulum stress / positive regulation of alpha-beta T cell proliferation / C-C chemokine receptor activity / NFE2L2 regulating inflammation associated genes / chemokine-mediated signaling pathway / negative regulation of adenylate cyclase activity / C-C chemokine binding / eosinophil chemotaxis / cellular homeostasis / positive regulation of monocyte chemotaxis / negative regulation of vascular endothelial cell proliferation / chemokine activity / Chemokine receptors bind chemokines / dendritic cell chemotaxis / regulation of T cell differentiation / negative regulation of G1/S transition of mitotic cell cycle / Interleukin-10 signaling / positive regulation of macrophage chemotaxis / positive regulation of calcium ion import / chemoattractant activity / macrophage chemotaxis / monocyte chemotaxis / hemopoiesis / humoral immune response / cellular response to interleukin-1 / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / cellular response to fibroblast growth factor stimulus / blood vessel remodeling / positive regulation of endothelial cell apoptotic process / cell surface receptor signaling pathway via JAK-STAT / cellular defense response / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / homeostasis of number of cells within a tissue / sensory perception of pain / cytoskeleton organization / cellular response to forskolin / positive regulation of interleukin-2 production / regulation of mitotic spindle organization / positive regulation of synaptic transmission, glutamatergic / viral genome replication / negative regulation of angiogenesis / animal organ morphogenesis / cell chemotaxis / Regulation of insulin secretion / response to bacterium / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / calcium-mediated signaling / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cytokine-mediated signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / cellular response to type II interferon / response to peptide hormone / G-protein beta/gamma-subunit complex binding / response to wounding / centriolar satellite / positive regulation of T cell activation / Olfactory Signaling Pathway / Activation of the phototransduction cascade 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: 2.9 Å | |||||||||||||||||||||
![]() | Shao, Z. / Tan, Y. / Shen, Q. / Yao, B. / Hou, L. / Qin, J. / Xu, P. / Mao, C. / Chen, L. / Zhang, H. ...Shao, Z. / Tan, Y. / Shen, Q. / Yao, B. / Hou, L. / Qin, J. / Xu, P. / Mao, C. / Chen, L. / Zhang, H. / Shen, D. / Zhang, C. / Li, W. / Du, X. / Li, F. / Chen, Z. / Jiang, Y. / Xu, H.E. / Ying, S. / Ma, H. / Zhang, Y. / Shen, H. | |||||||||||||||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3. 著者: Zhehua Shao / Yangxia Tan / Qingya Shen / Li Hou / Bingpeng Yao / Jiao Qin / Peiyu Xu / Chunyou Mao / Li-Nan Chen / Huibing Zhang / Dan-Dan Shen / Chao Zhang / Weijie Li / Xufei Du / Fei Li / ...著者: Zhehua Shao / Yangxia Tan / Qingya Shen / Li Hou / Bingpeng Yao / Jiao Qin / Peiyu Xu / Chunyou Mao / Li-Nan Chen / Huibing Zhang / Dan-Dan Shen / Chao Zhang / Weijie Li / Xufei Du / Fei Li / Zhi-Hua Chen / Yi Jiang / H Eric Xu / Songmin Ying / Honglei Ma / Yan Zhang / Huahao Shen / ![]() 要旨: Chemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC ...Chemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC chemokine receptor-G-protein complexes: CCR2 bound to its endogenous ligand CCL2, and CCR3 in the apo state. The structure of the CCL2-CCR2-G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, and forms substantial interactions with the receptor through the most N-terminal glutamine. Extensive hydrophobic and polar interactions are present between both two chemokine receptors and the Gα-protein, contributing to the constitutive activity of these receptors. Notably, complemented with functional experiments, the interactions around intracellular loop 2 of the receptors are found to be conserved and play a more critical role in G-protein activation than those around intracellular loop 3. Together, our findings provide structural insights into chemokine recognition and receptor activation, shedding lights on drug design targeting chemokine receptors. | |||||||||||||||||||||
履歴 |
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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 | ![]() | 228.9 KB | 表示 | ![]() |
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PDB形式 | ![]() | 176.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 33086MC ![]() 7x9yC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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
-タンパク質 , 2種, 2分子 RL
#1: タンパク質 | 分子量: 41104.332 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: P41597 |
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#2: タンパク質 | 分子量: 7913.181 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: P13500 |
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABC
#3: 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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#4: タンパク質 | 分子量: 39597.230 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 |
#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) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P59768 |
-抗体 , 1種, 1分子 E
#6: 抗体 | 分子量: 27370.510 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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-詳細
Has protein modification | 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: Cryo-EM structure of the apo CCR3-Gi complex / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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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 | 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 |
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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 / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 62 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.16_3549: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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: 142391 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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