登録情報 データベース : EMDB / ID : EMD-12746 構造の表示 ダウンロードとリンクタイトル Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist マップデータ 詳細 試料複合体 : [6P4]CCL5-CCR5-Gi-Fab16複合体 : Guanine nucleotide-binding protein G(i) subunit alpha-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1複合体 : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1複合体 : C-C chemokine receptor type 5タンパク質・ペプチド : C-C chemokine receptor type 5複合体 : Guanine nucleotide-binding protein G(T) subunit gamma-T1タンパク質・ペプチド : Guanine nucleotide-binding protein G(T) subunit gamma-T1複合体 : C-C motif chemokine 5(0-68)タンパク質・ペプチド : C-C motif chemokine 5複合体 : Fabタンパク質・ペプチド : Fab antibody fragment heavy chainタンパク質・ペプチド : Fab antibody fragment light chain 残り2件を表示 表示を減らす 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
regulation of chronic inflammatory response / CCR4 chemokine receptor binding / chemokine receptor antagonist activity / activation of phospholipase D activity / chemokine (C-C motif) ligand 5 binding / positive regulation of cellular biosynthetic process / CCR1 chemokine receptor binding / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / chemokine receptor binding ... regulation of chronic inflammatory response / CCR4 chemokine receptor binding / chemokine receptor antagonist activity / activation of phospholipase D activity / chemokine (C-C motif) ligand 5 binding / positive regulation of cellular biosynthetic process / CCR1 chemokine receptor binding / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / chemokine receptor binding / signaling / positive regulation of cell-cell adhesion mediated by integrin / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / chemokine receptor activity / positive regulation of activation of Janus kinase activity / receptor signaling protein tyrosine kinase activator activity / CCR5 chemokine receptor binding / positive regulation of T cell chemotaxis / positive regulation of homotypic cell-cell adhesion / negative regulation of G protein-coupled receptor signaling pathway / CCR chemokine receptor binding / lymphocyte chemotaxis / Inactivation, recovery and regulation of the phototransduction cascade / Activation of the phototransduction cascade / phosphatidylinositol phospholipase C activity / C-C chemokine receptor activity / negative regulation of T cell apoptotic process / positive regulation of T cell apoptotic process / C-C chemokine binding / neutrophil activation / positive regulation of calcium ion transport / eosinophil chemotaxis / response to cholesterol / positive regulation of innate immune response / cellular response to fibroblast growth factor stimulus / chemokine-mediated signaling pathway / positive regulation of monocyte chemotaxis / Chemokine receptors bind chemokines / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / chemokine activity / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / dendritic cell chemotaxis / Ca2+ pathway / regulation of T cell activation / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / leukocyte cell-cell adhesion / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of viral genome replication / phospholipase activator activity / positive regulation of macrophage chemotaxis / positive regulation of smooth muscle cell migration / exocytosis / chemoattractant activity / macrophage chemotaxis / Interleukin-10 signaling / monocyte chemotaxis / regulation of insulin secretion / positive regulation of cell adhesion / negative regulation by host of viral transcription / Adenylate cyclase inhibitory pathway / positive regulation of T cell migration / positive regulation of protein localization to cell cortex / positive regulation of translational initiation / positive regulation of viral genome replication / Binding and entry of HIV virion / cellular response to interleukin-1 / regulation of cAMP-mediated signaling / cellular defense response / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / coreceptor activity / positive regulation of T cell proliferation / positive regulation of phosphorylation / positive regulation of tyrosine phosphorylation of STAT protein / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway 類似検索 - 分子機能 CC chemokine receptor 5 / Chemokine receptor family / CC chemokine, conserved site / Small cytokines (intercrine/chemokine) C-C subfamily signature. / Chemokine beta/gamma/delta / Intercrine alpha family (small cytokine C-X-C) (chemokine CXC). / Chemokine interleukin-8-like domain / Chemokine interleukin-8-like superfamily / Small cytokines (intecrine/chemokine), interleukin-8 like / G-protein alpha subunit, group I ... CC chemokine receptor 5 / Chemokine receptor family / CC chemokine, conserved site / Small cytokines (intercrine/chemokine) C-C subfamily signature. / Chemokine beta/gamma/delta / Intercrine alpha family (small cytokine C-X-C) (chemokine CXC). / Chemokine interleukin-8-like domain / Chemokine interleukin-8-like superfamily / Small cytokines (intecrine/chemokine), interleukin-8 like / G-protein alpha subunit, group I / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Guanine nucleotide-binding protein G(T) subunit gamma-T1 / C-C motif chemokine 5 / C-C chemokine receptor type 5 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Bos taurus (ウシ) / Mus musculus (ハツカネズミ) / Bovine (ウシ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.15 Å 詳細 データ登録者Isaikina P / Tsai C-J / Dietz NB / Pamula F / Goldie KN / Schertler GFX / Maier T / Stahlberg H / Deupi X / Grzesiek S 資金援助 スイス, European Union, 4件 詳細 詳細を隠すOrganization Grant number 国 Swiss National Science Foundation 31-149927 スイス Swiss National Science Foundation 31-173089 スイス European Commission 6th Framework EMPRO European Union European Commission 7th Framework CHAARM European Union
引用ジャーナル : Sci Adv / 年 : 2021タイトル : Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist.著者: Polina Isaikina / Ching-Ju Tsai / Nikolaus Dietz / Filip Pamula / Anne Grahl / Kenneth N Goldie / Ramon Guixà-González / Camila Branco / Marianne Paolini-Bertrand / Nicolas Calo / Fabrice ... 著者 : Polina Isaikina / Ching-Ju Tsai / Nikolaus Dietz / Filip Pamula / Anne Grahl / Kenneth N Goldie / Ramon Guixà-González / Camila Branco / Marianne Paolini-Bertrand / Nicolas Calo / Fabrice Cerini / Gebhard F X Schertler / Oliver Hartley / Henning Stahlberg / Timm Maier / Xavier Deupi / Stephan Grzesiek / 要旨 : The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug ... The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug target, the molecular activation mechanism of CCR5, i.e., how chemokine agonists transduce the activation signal through the receptor, is yet unknown. Here, we report the cryo-EM structure of wild-type CCR5 in an active conformation bound to the chemokine super-agonist [6P4]CCL5 and the heterotrimeric G protein. The structure provides the rationale for the sequence-activity relation of agonist and antagonist chemokines. The N terminus of agonist chemokines pushes onto specific structural motifs at the bottom of the orthosteric pocket that activate the canonical GPCR microswitch network. This activation mechanism differs substantially from other CC chemokine receptors that bind chemokines with shorter N termini in a shallow binding mode involving unique sequence signatures and a specialized activation mechanism. 履歴 登録 2021年4月13日 - ヘッダ(付随情報) 公開 2021年6月30日 - マップ公開 2021年6月30日 - 更新 2022年3月16日 - 現状 2022年3月16日 処理サイト : PDBe / 状態 : 公開
すべて表示 表示を減らす