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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of CXCL8 bound C-X-C chemokine receptor 1 in complex with Gi heterotrimer | |||||||||
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![]() | GPCR / Chemokine / Interleukin / CXCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | ![]() interleukin-8 receptor activity / 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 binding / positive regulation of cellular biosynthetic process / chemokine receptor activity / negative regulation of cell adhesion molecule production / negative regulation of G protein-coupled receptor signaling pathway / ATF4 activates genes in response to endoplasmic reticulum stress ...interleukin-8 receptor activity / 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 binding / positive regulation of cellular biosynthetic process / chemokine receptor activity / negative regulation of cell adhesion molecule production / negative regulation of G protein-coupled receptor signaling pathway / ATF4 activates genes in response to endoplasmic reticulum stress / CXCR chemokine receptor binding / embryonic digestive tract development / induction of positive chemotaxis / C-C chemokine receptor activity / C-C chemokine binding / neutrophil activation / cellular response to fibroblast growth factor stimulus / chemokine-mediated signaling pathway / positive regulation of neutrophil chemotaxis / Chemokine receptors bind chemokines / chemokine activity / dendritic cell chemotaxis / Interleukin-10 signaling / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / cellular response to interleukin-1 / 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 / response to endoplasmic reticulum stress / Peptide ligand-binding receptors / neutrophil chemotaxis / secretory granule membrane / Regulation of insulin secretion / G protein-coupled receptor activity / G protein-coupled receptor binding / calcium-mediated signaling / 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 / response to molecule of bacterial origin / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / receptor internalization / 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 / antimicrobial humoral immune response mediated by antimicrobial peptide / 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 / cellular response to tumor necrosis factor / heparin binding / cell cortex / midbody / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / Senescence-Associated Secretory Phenotype (SASP) 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: 3.41 Å | |||||||||
![]() | Ishimoto N / Park JH / Park SY | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis of CXC chemokine receptor 1 ligand binding and activation. 著者: Naito Ishimoto / Jae-Hyun Park / Kouki Kawakami / Michiko Tajiri / Kenji Mizutani / Satoko Akashi / Jeremy R H Tame / Asuka Inoue / Sam-Yong Park / ![]() 要旨: Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and ...Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers. These GPCRs have therefore been the target of many drug development campaigns and structural studies. Here, we solve the structure of CXCR1 complexed with CXCL8 and cognate G-proteins using cryo-EM, showing the detailed interactions between the receptor, the chemokine and Gαi protein. Unlike the closely related CXCR2, CXCR1 strongly prefers to bind CXCL8 in its monomeric form. The model shows that steric clashes would form between dimeric CXCL8 and extracellular loop 2 (ECL2) of CXCR1. Consistently, transplanting ECL2 of CXCR2 onto CXCR1 abolishes the selectivity for the monomeric chemokine. Our model and functional analysis of various CXCR1 mutants will assist efforts in structure-based drug design targeting specific CXC chemokine receptor subtypes. | |||||||||
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 | ![]() | 28 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 28.5 KB 28.5 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 6.5 KB | 表示 | ![]() |
画像 | ![]() | 51.5 KB | ||
マスクデータ | ![]() | 29.6 MB | ![]() | |
その他 | ![]() ![]() ![]() ![]() | 26.3 MB 14.8 MB 27.5 MB 27.5 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 840.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 839.9 KB | 表示 | |
XML形式データ | ![]() | 13.8 KB | 表示 | |
CIF形式データ | ![]() | 17.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8ic0MC 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 ( |
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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
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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マップ
ファイル | ![]() | ||||||||||||||||||||
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注釈 | sharpened map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.07313 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
-マスク #1
ファイル | ![]() | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: The map was calculated by deepEMhancer
ファイル | emd_35351_additional_1.map | ||||||||||||
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注釈 | The map was calculated by deepEMhancer | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: map
ファイル | emd_35351_additional_2.map | ||||||||||||
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注釈 | map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map 1
ファイル | emd_35351_half_map_1.map | ||||||||||||
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注釈 | half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map 2
ファイル | emd_35351_half_map_2.map | ||||||||||||
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注釈 | half map 2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Cryo-EM structure of human chemokine receptor 1
全体 | 名称: Cryo-EM structure of human chemokine receptor 1 |
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要素 |
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-超分子 #1: Cryo-EM structure of human chemokine receptor 1
超分子 | 名称: Cryo-EM structure of human chemokine receptor 1 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 150 KDa |
-分子 #1: C-X-C chemokine receptor type 1
分子 | 名称: C-X-C chemokine receptor type 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: 40.935199 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSNITDPQMW DFDDLNFTGM PPADEDYSPC MLETETLNKY VVIIAYALVF LLSLLGNSLV MLVILYSRVG RSVTDVYLLN LALADLLFA LTLPIWAASK VNGWIFGTFL CKVVSLLKEV NFYSGILLLA CISVDRYLAI VHATRTLTQK RHLVKFVCLG C WGLSMNLS ...文字列: MSNITDPQMW DFDDLNFTGM PPADEDYSPC MLETETLNKY VVIIAYALVF LLSLLGNSLV MLVILYSRVG RSVTDVYLLN LALADLLFA LTLPIWAASK VNGWIFGTFL CKVVSLLKEV NFYSGILLLA CISVDRYLAI VHATRTLTQK RHLVKFVCLG C WGLSMNLS LPFFLFRQAY HPNNSSPVCY EVLGNDTAKW RMVLRILPHT FGFIVPLFVM LFCYGFTLRT LFKAHMGQKH RA MRVIFAV VLIFLLCWLP YNLVLLADTL MRTQVIQESC ERRNNIGRAL DATEILGFLH SCLNPIIYAF IGQNFRHGFL KIL AMHGLV SKEFLARHRV TSYTSSSVNV SSNLHHHHHH HH UniProtKB: C-X-C chemokine receptor type 1 |
-分子 #2: 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: 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: 40.415031 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #3: 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: 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: 37.728152 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GPGSSGSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...文字列: GPGSSGSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #4: 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: 4 / 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: 8.506765 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: scFv16
分子 | 名称: scFv16 / 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: 27.409588 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 KAAALEVLFQ |
-分子 #6: Interleukin-8
分子 | 名称: Interleukin-8 / 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: 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 |
-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 | 1.0 mg/mL | ||||||||||||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
詳細: 50 mM HEPES pH8.0, 100 mM NaCl, 1 mM MgCl2, 0.5 mM TCEP, 0.001% LMNG, 0.0001% CHS, 1 uM IL8 | ||||||||||||||||||||||||
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / 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: 60 sec. | ||||||||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 298 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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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 4175 / 平均露光時間: 4.7 sec. / 平均電子線量: 51.16 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 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): 1.6 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 105000 |
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 |
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画像解析
-原子モデル構築 1
精密化 | 空間: REAL |
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得られたモデル | ![]() PDB-8ic0: |