+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33107 | ||||||||||||
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タイトル | Cryo-EM structure of the human chemokine receptor CX3CR1 in complex with Gi1 | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | G protein-coupled receptor / chemokine receptor / CX3CR1 / SIGNALING PROTEIN | ||||||||||||
機能・相同性 | 機能・相同性情報 C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / macropinosome membrane / C-X3-C chemokine binding / regulation of microglial cell migration / CX3C chemokine receptor binding / negative regulation of hippocampal neuron apoptotic process / microglial cell activation involved in immune response ...C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / macropinosome membrane / C-X3-C chemokine binding / regulation of microglial cell migration / CX3C chemokine receptor binding / negative regulation of hippocampal neuron apoptotic process / microglial cell activation involved in immune response / host-mediated regulation of intestinal microbiota composition / autocrine signaling / synapse pruning / central nervous system maturation / positive regulation of microglial cell migration / synapse maturation / antifungal innate immune response / chemokine receptor activity / positive regulation of I-kappaB phosphorylation / C-C chemokine receptor activity / leukocyte tethering or rolling / C-C chemokine binding / regulation of tumor necrosis factor production / G protein-coupled peptide receptor activity / positive regulation of monocyte chemotaxis / leukocyte chemotaxis / regulation of nitric oxide biosynthetic process / Chemokine receptors bind chemokines / positive regulation of neurogenesis / negative regulation of interleukin-1 beta production / positive regulation of neuroblast proliferation / RSV-host interactions / neuronal cell body membrane / Respiratory syncytial virus (RSV) attachment and entry / social behavior / negative regulation of apoptotic signaling pathway / regulation of neurogenesis / negative regulation of long-term synaptic potentiation / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / cellular defense response / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / cellular response to transforming growth factor beta stimulus / regulation of mitotic spindle organization / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / cell chemotaxis / negative regulation of cell migration / response to ischemia / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / brain development / modulation of chemical synaptic transmission / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / regulation of synaptic plasticity / 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 / memory / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / 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 / response to wounding / 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 / positive regulation of angiogenesis / 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 / chemotaxis / GDP binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding 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: 2.8 Å | ||||||||||||
データ登録者 | Lu M / Zhao W / Han S / Zhu Y / Wu B / Zhao Q | ||||||||||||
資金援助 | 中国, 3件
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引用 | ジャーナル: Sci Adv / 年: 2022 タイトル: Activation of the human chemokine receptor CX3CR1 regulated by cholesterol. 著者: Minmin Lu / Wenli Zhao / Shuo Han / Xiaowen Lin / Tingyu Xu / Qiuxiang Tan / Mu Wang / Cuiying Yi / Xiaojing Chu / Weibo Yang / Ya Zhu / Beili Wu / Qiang Zhao / 要旨: As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and ...As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-G complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-Å resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-G complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling. | ||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_33107.map.gz | 59.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33107-v30.xml emd-33107.xml | 18.5 KB 18.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_33107.png | 126.5 KB | ||
Filedesc metadata | emd-33107.cif.gz | 6.1 KB | ||
その他 | emd_33107_half_map_1.map.gz emd_33107_half_map_2.map.gz | 49.6 MB 49.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33107 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33107 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33107_validation.pdf.gz | 793.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33107_full_validation.pdf.gz | 793.1 KB | 表示 | |
XML形式データ | emd_33107_validation.xml.gz | 12.1 KB | 表示 | |
CIF形式データ | emd_33107_validation.cif.gz | 14.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33107 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33107 | HTTPS FTP |
-関連構造データ
関連構造データ | 7xbwMC 7xbxC M: このマップから作成された原子モデル 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
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_33107.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: 1.045 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #1
ファイル | emd_33107_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_33107_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Chemokine receptor CX3CR1 in complex with Gi1
全体 | 名称: Chemokine receptor CX3CR1 in complex with Gi1 |
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要素 |
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-超分子 #1: Chemokine receptor CX3CR1 in complex with Gi1
超分子 | 名称: Chemokine receptor CX3CR1 in complex with Gi1 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 40.447141 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVTAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 38.245805 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: HHHHHHMSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSAS QDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT GYLSCCRFLD D NQIVTSSG ...文字列: HHHHHHMSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSAS QDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT GYLSCCRFLD D NQIVTSSG DTTCALWDIE TGQQTTTFTG HTGDVMSLSL APDTRLFVSG ACDASAKLWD VREGMCRQTF TGHESDINAI CF FPNGNAF ATGSDDATCR LFDLRADQEL MTYSHDNIIC GITSVSFSKS GRLLLAGYDD FNCNVWDALK ADRAGVLAGH DNR VSCLGV TDDGMAVATG SWDSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: CX3C chemokine receptor 1
分子 | 名称: CX3C chemokine receptor 1 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 41.07268 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL LVVFALTNSK KPKSVTDIYL LNLALSDLLF VATLPFWTH YLINEKGLHN AMCKFTTAFF FIGFFGSIFF LTVISIDRYL AIVLAANSMN NRTVQHGVTI SLGVWAAAIL V AAPQFMFT ...文字列: MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL LVVFALTNSK KPKSVTDIYL LNLALSDLLF VATLPFWTH YLINEKGLHN AMCKFTTAFF FIGFFGSIFF LTVISIDRYL AIVLAANSMN NRTVQHGVTI SLGVWAAAIL V AAPQFMFT KQKENECLGD YPEVLQEIWP VLRNVETNFL GFLLPLLIMS YCYFRIIQTL FSSKNHKKAK AIKLILLVVI VF FLFWTPY NVVIFLETLK LYDFFPSCDM RKDLRLALSV TETVAFSHCC LNPLIYAFAG EKFRRYLYHL YGKCLAVLEF LEV LFQGPW SHPQFEKGGG SGGGSGGSAW SHPQFEKDYK DDDDK UniProtKB: CX3C chemokine receptor 1 |
-分子 #5: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 5 / コピー数: 3 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-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 | particle |
-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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 2.1875 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: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: INSILICO MODEL |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 702722 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |