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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structure of a class A GPCR/agonist complex | |||||||||
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![]() | GPCR / agonist / STRUCTURAL PROTEIN | |||||||||
機能・相同性 | ![]() chemokine receptor activity / CCR chemokine receptor binding / C-C chemokine receptor activity / chemokine-mediated signaling pathway / C-C chemokine binding / eosinophil chemotaxis / positive regulation of monocyte chemotaxis / chemokine activity / Chemokine receptors bind chemokines / positive regulation of interleukin-17 production ...chemokine receptor activity / CCR chemokine receptor binding / C-C chemokine receptor activity / chemokine-mediated signaling pathway / C-C chemokine binding / eosinophil chemotaxis / positive regulation of monocyte chemotaxis / chemokine activity / Chemokine receptors bind chemokines / positive regulation of interleukin-17 production / viral process / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / coreceptor activity / 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 / bioluminescence / generation of precursor metabolites and energy / 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 / 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 / intracellular calcium ion homeostasis / 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 / positive regulation of inflammatory response / 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 / 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 / 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 / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / G protein activity / positive regulation of cytosolic calcium ion concentration / GTPase binding / retina development in camera-type eye / Ca2+ pathway / 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 / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / cell adhesion / ciliary basal body / immune response / positive regulation of cell migration / G protein-coupled receptor signaling pathway / inflammatory response 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: 3.1 Å | |||||||||
![]() | Sun D / Johnson M / Masureel M | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8. 著者: Dawei Sun / Yonglian Sun / Eric Janezic / Tricia Zhou / Matthew Johnson / Caleigh Azumaya / Sigrid Noreng / Cecilia Chiu / Akiko Seki / Teresita L Arenzana / John M Nicoludis / Yongchang Shi ...著者: Dawei Sun / Yonglian Sun / Eric Janezic / Tricia Zhou / Matthew Johnson / Caleigh Azumaya / Sigrid Noreng / Cecilia Chiu / Akiko Seki / Teresita L Arenzana / John M Nicoludis / Yongchang Shi / Baomei Wang / Hoangdung Ho / Prajakta Joshi / Christine Tam / Jian Payandeh / Laëtitia Comps-Agrar / Jianyong Wang / Sascha Rutz / James T Koerber / Matthieu Masureel / ![]() 要旨: The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an ...The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an attractive therapeutic approach, but the molecular basis for chemokine-mediated activation and antibody-mediated inhibition of CCR8 are not fully elucidated. Here, we obtain an antagonist antibody against human CCR8 and determine structures of CCR8 in complex with either the antibody or the endogenous agonist ligand CCL1. Our studies reveal characteristic antibody features allowing recognition of the CCR8 extracellular loops and CCL1-CCR8 interaction modes that are distinct from other chemokine receptor - ligand pairs. Informed by these structural insights, we demonstrate that CCL1 follows a two-step, two-site binding sequence to CCR8 and that antibody-mediated inhibition of CCL1 signaling can occur by preventing the second binding event. Together, our results provide a detailed structural and mechanistic framework of CCR8 activation and inhibition that expands our molecular understanding of chemokine - receptor interactions and offers insight into the development of therapeutic antibodies targeting chemokine GPCRs. | |||||||||
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構造の表示
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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 | ![]() | 43.5 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 17.2 KB 17.2 KB | 表示 表示 | ![]() |
画像 | ![]() | 76.7 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
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 | ![]() 8u1uMC ![]() 8tlmC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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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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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: 1.0153 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 : CCR8 in complex with CCL1 and Gi
全体 | 名称: CCR8 in complex with CCL1 and Gi |
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要素 |
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-超分子 #1: CCR8 in complex with CCL1 and Gi
超分子 | 名称: CCR8 in complex with CCL1 and Gi / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: ![]() |
-分子 #1: C-C motif chemokine 1,C-C chemokine receptor type 8,EGFP fusion p...
分子 | 名称: C-C motif chemokine 1,C-C chemokine receptor type 8,EGFP fusion protein 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: 83.23668 KDa |
組換発現 | 生物種: Mammalian expression vector Flag-MCS-pcDNA3.1 (その他) |
配列 | 文字列: KSMQVPFSRC CFSFCEQEIP LRAILCYRNT SSICSNEGLI FKLKRGKEAC ALDTVGWVQR HRKMLRHCPS KRKGSGSGSG SGSGSGSGS GSGSGSGSDY TLDLSVTTVT DYYYPDICSS PCDAELIQTN GKLLLAVFYC LLFVFSLLGN SLVILVLVVC K KLRSITDV ...文字列: KSMQVPFSRC CFSFCEQEIP LRAILCYRNT SSICSNEGLI FKLKRGKEAC ALDTVGWVQR HRKMLRHCPS KRKGSGSGSG SGSGSGSGS GSGSGSGSDY TLDLSVTTVT DYYYPDICSS PCDAELIQTN GKLLLAVFYC LLFVFSLLGN SLVILVLVVC K KLRSITDV YLLNLALSDL LFVFSFPFQT YYLLDQWVFG TVMCKVVSGF YYIGFYSSMF FITLMSVDRY LAVVHAVYAL KV RTIRMGT TLCLAVWLTA IMATIPLLVF YQVASEDGVL QCYSFYNQQT LKWKIFTNFK MNILGLLIPF TIFMFCYIKI LHQ LKRCQN HNKTKAIRLV LIVVIASLLF WVPFNVVLFL TSLHSMHILD GCSISQQLTY ATHVTEIISF THCCVNPVIY AFVG EKFKK HLSEIFQKSC SQIFNYLGRQ MPRESCEKSS SCQQHSSRSS SVDYILGGSD YKDDDDKGGS LEVLFQGPMV SKGEE LFTG VVPILVELDG DVNGHKFSVS GEGEGDATYG KLTLKLICTT GKLPVPWPTL VTTLGYGLQC FARYPDHMKQ HDFFKS AMP EGYVQERTIF FKDDGNYKTR AEVKFEGDTL VNRIELKGID FKEDGNILGH KLEYNYNSHN VYITADKQKN GIKANFK IR HNIEDGGVQL ADHYQQNTPI GDGPVLLPDN HYLSYQSKLS KDPNEKRDHM VLLEFVTAAG ITLGMDELYK GSAWSHPQ F EKGGGSGGGS GGSAWSHPQF EK UniProtKB: C-C motif chemokine 1, C-C chemokine receptor type 8, EGFP |
-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: 43.182078 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKKHHHHHHH HHHENLYFQG GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECK QYKAVVYSNT IQSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ A CFNRSREY ...文字列: MKKHHHHHHH HHHENLYFQG GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECK QYKAVVYSNT IQSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ A CFNRSREY QLNDSAAYYL NDLDRIAQPN YIPTQQDVLR TRVKTTGIVE THFTFKDLHF KMFDVGGQRS ERKKWIHCFE GV TAIIFCV ALSDYDLVLA EDEEMNRMHE SMKLFDSICN NKWFTDTSII LFLNKKDLFE EKIKKSPLTI CYPEYAGSNT YEE AAAYIQ CQFEDLNKRK DTKEIYTHFT CATDTKNVQF VFDAVTDVII KNNLKDCGLF 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: 39.518121 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHHHG ENLYFQGSSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF ...文字列: MHHHHHHHHG ENLYFQGSSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF LDDNQIVTSS GDTTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FT GHESDIN AICFFPNGNA FATGSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KAD RAGVLA GHDNRVSCLG VTDDGMAVAT GSWDSFLKIW N 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: 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 #5: scFv fragment
分子 | 名称: scFv fragment / 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: 28.124387 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: AGSDVQLVES GGGLVQPGGS RKLSCSASGF AFSSFGMHWV RQAPEKGLEW VAYISSGSGT IYYADTVKGR FTISRDDPKN TLFLQMTSL RSEDTAMYYC VRSIYYYGSS PFDFWGQGTT LTVSSGGSDI VMTQATSSVP VTPGESVSIS CRSSKSLLHS N GNTYLYWF ...文字列: AGSDVQLVES GGGLVQPGGS RKLSCSASGF AFSSFGMHWV RQAPEKGLEW VAYISSGSGT IYYADTVKGR FTISRDDPKN TLFLQMTSL RSEDTAMYYC VRSIYYYGSS PFDFWGQGTT LTVSSGGSDI VMTQATSSVP VTPGESVSIS CRSSKSLLHS N GNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TFGAGTKLEL KA AAGNSLV PRGSHHHHHH HH |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / コピー数: 1 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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 |
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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: FEI FALCON IV (4k x 4k) 平均電子線量: 40.814 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 / 最大 デフォーカス(公称値): 1.8 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 |
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画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.1 Å / 解像度の算出法: OTHER / 使用した粒子像数: 201761 |
初期 角度割当 | タイプ: OTHER / 詳細: Ab initio in cryoSPARC |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |