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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of the CCL15(27-92) bound CCR1-Gi complex | |||||||||
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![]() | GPCR / CCR1 / Chemokine Receptor / MEMBRNE PROTEIN / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() chemokine (C-C motif) ligand 7 binding / chemokine (C-C motif) ligand 5 binding / chemokine receptor activity / CCR chemokine receptor binding / negative regulation of bone mineralization / C-C chemokine receptor activity / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / chemokine-mediated signaling pathway / C-C chemokine binding / positive regulation of calcium ion transport ...chemokine (C-C motif) ligand 7 binding / chemokine (C-C motif) ligand 5 binding / chemokine receptor activity / CCR chemokine receptor binding / negative regulation of bone mineralization / C-C chemokine receptor activity / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / chemokine-mediated signaling pathway / C-C chemokine binding / positive regulation of calcium ion transport / positive regulation of osteoclast differentiation / positive regulation of monocyte chemotaxis / chemokine activity / Chemokine receptors bind chemokines / dendritic cell chemotaxis / Interleukin-10 signaling / chemoattractant activity / exocytosis / monocyte chemotaxis / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / 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 / cellular response to forskolin / regulation of mitotic spindle organization / cell chemotaxis / Regulation of insulin secretion / 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 / response to peptide hormone / G-protein beta/gamma-subunit complex binding / response to wounding / 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 / intracellular calcium ion homeostasis / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / antimicrobial humoral immune response mediated by antimicrobial peptide / 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) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / chemotaxis / photoreceptor disc membrane / calcium ion transport / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / 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 / sensory perception of taste / cell-cell signaling / extracellular vesicle / heparin binding / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / G protein activity / GTPase binding / positive regulation of cytosolic calcium ion concentration / Ca2+ pathway / retina development in camera-type eye / midbody / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway 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: 2.7 Å | |||||||||
![]() | Shao Z / Shen Q | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1. 著者: Zhehua Shao / Qingya Shen / Bingpeng Yao / Chunyou Mao / Li-Nan Chen / Huibing Zhang / Dan-Dan Shen / Chao Zhang / Weijie Li / Xufei Du / Fei Li / Honglei Ma / Zhi-Hua Chen / H Eric Xu / ...著者: Zhehua Shao / Qingya Shen / Bingpeng Yao / Chunyou Mao / Li-Nan Chen / Huibing Zhang / Dan-Dan Shen / Chao Zhang / Weijie Li / Xufei Du / Fei Li / Honglei Ma / Zhi-Hua Chen / H Eric Xu / Songmin Ying / Yan Zhang / Huahao Shen / ![]() 要旨: Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and ...Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-G complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y291) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of β-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine-receptor complexes, providing new insights into the mode of chemokine recognition. | |||||||||
履歴 |
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構造の表示
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マップデータ | ![]() | 28.5 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.9 KB 16.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 113 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
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
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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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: 1.014 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
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試料の構成要素
-全体 : CCL15(27-92)-bound CCR1-Gi complex
全体 | 名称: CCL15(27-92)-bound CCR1-Gi complex |
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要素 |
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-超分子 #1: CCL15(27-92)-bound CCR1-Gi complex
超分子 | 名称: CCL15(27-92)-bound CCR1-Gi complex / 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 #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: 40.414047 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER 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: ![]() |
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 #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: CCL15(27-92)
分子 | 名称: CCL15(27-92) / 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: 8.218506 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: HFAADCCTSY ISQSIPCSLM KSYFETSSEC SKPGVIFLTK KGRQVCAKPS GPGVQDCMKK LKPYSIGSGE NLYFQ UniProtKB: C-C motif chemokine 15 |
-分子 #5: C-C chemokine receptor type 1
分子 | 名称: C-C chemokine receptor type 1 / 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: 42.203547 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GGSGMETPNT TEDYDTTTEF DYGDATPCQK VNERAFGAQL LPPLYSLVFV IGLVGNILVV LVLVQYKRLK NMTSIYLLNL AISDLLFLF TLPFWIDYKL KDDWVFGDAM CKILSGFYYT GLYSEIFFII LLTIDRYLAI VHAVFALRAR TVTFGVITSI I IWALAILA ...文字列: GGSGMETPNT TEDYDTTTEF DYGDATPCQK VNERAFGAQL LPPLYSLVFV IGLVGNILVV LVLVQYKRLK NMTSIYLLNL AISDLLFLF TLPFWIDYKL KDDWVFGDAM CKILSGFYYT GLYSEIFFII LLTIDRYLAI VHAVFALRAR TVTFGVITSI I IWALAILA SMPGLYFSKT QWEFTHHTCS LHFPHESLRE WKLFQALKLN LFGLVLPLLV MIICYTGIIK ILLRRPNEKK SK AVRLIFV IMIIFFLFWT PYNLTILISV FQDFLFTHEC EQSRHLDLAV QVTEVIAYTH CCVNPVIYAF VGERFRKYLR QLF HRRVAV HLVKWLPFLS VDRLERVSST SPSTGEHELS AGFLEVLFQ UniProtKB: C-C chemokine receptor type 1 |
-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: 27.340482 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 KGSLEVLFQ |
-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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE / 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 K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 62.0 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 423872 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |