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基本情報
登録情報 | データベース: EMDB / ID: EMD-0877 | |||||||||
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タイトル | Cryo-EM structure of a class A GPCR | |||||||||
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![]() | G protein coupled-receptor / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() regulation of single stranded viral RNA replication via double stranded DNA intermediate / regulation of entry of bacterium into host cell / interleukin-8 receptor binding / interleukin-8-mediated signaling pathway / metanephric tubule morphogenesis / negative regulation of neutrophil apoptotic process / mast cell granule / interleukin-8 receptor activity / interleukin-8 binding / acute inflammatory response to antigenic stimulus ...regulation of single stranded viral RNA replication via double stranded DNA intermediate / regulation of entry of bacterium into host cell / interleukin-8 receptor binding / interleukin-8-mediated signaling pathway / metanephric tubule morphogenesis / negative regulation of neutrophil apoptotic process / mast cell granule / interleukin-8 receptor activity / interleukin-8 binding / acute inflammatory response to antigenic stimulus / negative regulation of cell adhesion molecule production / CXCR chemokine receptor binding / C-X-C chemokine receptor activity / ATF4 activates genes in response to endoplasmic reticulum stress / embryonic digestive tract development / neutrophil activation / induction of positive chemotaxis / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of vascular permeability / chemokine activity / positive regulation of neutrophil chemotaxis / Chemokine receptors bind chemokines / dendritic cell chemotaxis / negative regulation of G protein-coupled receptor signaling pathway / midbrain development / Interleukin-10 signaling / cellular response to interleukin-1 / cellular response to fibroblast growth factor stimulus / cellular defense response / regulation of cell adhesion / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / positive regulation of cardiac muscle cell apoptotic process / 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 / neutrophil chemotaxis / cellular response to forskolin / regulation of mitotic spindle organization / response to endoplasmic reticulum stress / Peptide ligand-binding receptors / secretory granule membrane / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / calcium-mediated signaling / response to molecule of bacterial origin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled receptor activity / receptor internalization / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / G-protein beta/gamma-subunit complex binding / centriolar satellite / Olfactory 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 / antimicrobial humoral immune response mediated by antimicrobial peptide / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / positive regulation of angiogenesis / ADP signalling through P2Y purinoceptor 12 / chemotaxis / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / mitotic spindle / GDP binding / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / cellular response to tumor necrosis factor / sensory perception of taste / extracellular vesicle 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.5 Å | |||||||||
![]() | Liu ZJ / Hua T | |||||||||
![]() | ![]() タイトル: Structural basis of CXC chemokine receptor 2 activation and signalling. 著者: Kaiwen Liu / Lijie Wu / Shuguang Yuan / Meng Wu / Yueming Xu / Qianqian Sun / Shu Li / Suwen Zhao / Tian Hua / Zhi-Jie Liu / ![]() 要旨: Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions such as inflammation and cancer. Although ample effort has ...Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions such as inflammation and cancer. Although ample effort has been invested into the structural investigation of the chemokine receptors and receptor-chemokine recognition, less is known about endogenous chemokine-induced receptor activation and G-protein coupling. Here we present the cryo-electron microscopy structures of interleukin-8 (IL-8, also known as CXCL8)-activated human CXC chemokine receptor 2 (CXCR2) in complex with G protein, along with a crystal structure of CXCR2 bound to a designed allosteric antagonist. Our results reveal a unique shallow mode of binding between CXCL8 and CXCR2, and also show the interactions between CXCR2 and G protein. Further structural analysis of the inactive and active states of CXCR2 reveals a distinct activation process and the competitive small-molecule antagonism of chemokine receptors. In addition, our results provide insights into how a G-protein-coupled receptor is activated by an endogenous protein molecule, which will assist in the rational development of therapeutics that target the chemokine system for better pharmacological profiles. | |||||||||
履歴 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 25.5 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.5 KB 20.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 79.5 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1.38667 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
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試料の構成要素
-全体 : Ternary complex of chemokine, GPCR and G protein
全体 | 名称: Ternary complex of chemokine, GPCR and G protein |
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要素 |
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-超分子 #1: Ternary complex of chemokine, GPCR and G protein
超分子 | 名称: Ternary complex of chemokine, GPCR and G protein / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 150 KDa |
-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: ![]() |
分子量 | 理論値: 40.283836 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GCTLSAEDKA AVERSKMIDR NLREDGEKAA REVKLLLLGA GESGKSTIVK QMKIIHEAGY SEEECKQYKA VVYSNTIQSI IAIIRAMGR LKIDFGDSAR ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND SAAYYLNDLD R IAQPNYIP ...文字列: GCTLSAEDKA AVERSKMIDR NLREDGEKAA REVKLLLLGA GESGKSTIVK QMKIIHEAGY SEEECKQYKA VVYSNTIQSI IAIIRAMGR LKIDFGDSAR ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND SAAYYLNDLD R IAQPNYIP TQQDVLRTRV KTTGIVETHF TFKDLHFKMF DVGGQRSERK KWIHCFEGVT AIIFCVALSD YDLVLAEDEE MN RMHESMK LFDSICNNKW FTDTSIILFL NKKDLFEEKI KKSPLTICYP EYAGSNTYEE AAAYIQCQFE DLNKRKDTKE IYT HFTCAT DTKNVQFVFD AVTDVIIKNN LKDCGLF 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: ![]() |
分子量 | 理論値: 38.045629 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: IGRARGFSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSAS QDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT GYLSCCRFLD D NQIVTSSG ...文字列: IGRARGFSEL 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: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() ![]() |
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: Interleukin-8
分子 | 名称: Interleukin-8 / タイプ: protein_or_peptide / ID: 4 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 8.401807 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SAKELRCQCI KTYSKPFHPK FIKELRVIES GPHCANTEII VKLSDGRELC LDPKENWVQR VVEKFLKRAE NS UniProtKB: Interleukin-8 |
-分子 #5: C-X-C chemokine receptor type 2
分子 | 名称: C-X-C chemokine receptor type 2 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 40.798121 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MEDFNMESDS FEDFWKGEDL SNYSYSSTLP PFLLDAAPCE PESLEINKYF VVIIYALVFL LSLLGNSLVM LVILYSRVGR SVTDVYLLN LALADLLFAL TLPIWAASKV NGWIFGTFLC KVVSLLKEVN FYSGILLLAC ISVDRYLAIV HATRTLTQKR Y LVKFICLS ...文字列: MEDFNMESDS FEDFWKGEDL SNYSYSSTLP PFLLDAAPCE PESLEINKYF VVIIYALVFL LSLLGNSLVM LVILYSRVGR SVTDVYLLN LALADLLFAL TLPIWAASKV NGWIFGTFLC KVVSLLKEVN FYSGILLLAC ISVDRYLAIV HATRTLTQKR Y LVKFICLS IWGLSLLLAL PVLLFRRTVY SSNVSPACYE DMGNNTANWR MLLRILPQSF GFIVPLLIML FCYGFTLRTL FK AHMGQKH RAMRVIFAVV LIFLLCWLPY NLVLLADTLM RTQVIQETCE RRNHIDRALD ATEILGILHS CLNPLIYAFI GQK FRHGLL KILAIHGLIS KDSLPKDSRP SFVGSSSGHT STTL UniProtKB: C-X-C chemokine receptor type 2 |
-分子 #6: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 27.784896 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-分子 #7: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 1 / 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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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 1 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Homemade / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 40 sec. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - サイズ - 横: 7420 pixel / デジタル化 - サイズ - 縦: 7676 pixel / 撮影したグリッド数: 5 / 実像数: 15688 / 平均露光時間: 0.8 sec. / 平均電子線量: 8.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 50.0 µm / 最大 デフォーカス(補正後): 2.0 µm / 最小 デフォーカス(補正後): 0.8 µm / 倍率(補正後): 130000 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 130000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |