登録情報 データベース : EMDB / ID : EMD-14312 ダウンロードとリンクタイトル phospho-STING binding to adaptor protein complex-1 マップデータ 詳細 試料複合体 : phospho-STING binding to adaptor protein complex-1タンパク質・ペプチド : AP-1 complex subunit beta-1タンパク質・ペプチド : ADP-ribosylation factor 1タンパク質・ペプチド : AP-1 complex subunit gamma-1タンパク質・ペプチド : Stimulator of interferon genes proteinタンパク質・ペプチド : AP-1 complex subunit mu-1タンパク質・ペプチド : AP-1 complex subunit sigma-3 残り2件を表示 表示を減らすリガンド : GUANOSINE-5'-TRIPHOSPHATEリガンド : MAGNESIUM ION 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
basolateral protein secretion / mitotic cleavage furrow ingression / endosome to melanosome transport / trans-Golgi Network Vesicle Budding / AP-1 adaptor complex / Lysosome Vesicle Biogenesis / platelet dense granule organization / regulation of receptor internalization / Glycosphingolipid transport / melanosome assembly ... basolateral protein secretion / mitotic cleavage furrow ingression / endosome to melanosome transport / trans-Golgi Network Vesicle Budding / AP-1 adaptor complex / Lysosome Vesicle Biogenesis / platelet dense granule organization / regulation of receptor internalization / Glycosphingolipid transport / melanosome assembly / STING complex / regulation of Arp2/3 complex-mediated actin nucleation / Intra-Golgi traffic / Golgi to vacuole transport / STAT6-mediated induction of chemokines / Synthesis of PIPs at the Golgi membrane / Golgi Associated Vesicle Biogenesis / protein localization to endoplasmic reticulum / serine/threonine protein kinase complex / proton channel activity / clathrin adaptor activity / 2',3'-cyclic GMP-AMP binding / STING mediated induction of host immune responses / MHC class II antigen presentation / cyclic-di-GMP binding / Nef Mediated CD4 Down-regulation / IRF3-mediated induction of type I IFN / dendritic spine organization / positive regulation of type I interferon-mediated signaling pathway / cGAS/STING signaling pathway / determination of left/right symmetry / reticulophagy / long-term synaptic depression / pattern recognition receptor signaling pathway / clathrin-coated vesicle / COPI-dependent Golgi-to-ER retrograde traffic / Lysosome Vesicle Biogenesis / cytoplasmic pattern recognition receptor signaling pathway / clathrin binding / Golgi Associated Vesicle Biogenesis / cellular response to exogenous dsRNA / cell leading edge / Synthesis of PIPs at the plasma membrane / autophagosome membrane / antiviral innate immune response / positive regulation of macroautophagy / cellular response to organic cyclic compound / autophagosome assembly / intracellular copper ion homeostasis / autophagosome / positive regulation of type I interferon production / cellular response to interferon-beta / protein targeting / COPI-mediated anterograde transport / signaling adaptor activity / clathrin-coated pit / vesicle-mediated transport / positive regulation of defense response to virus by host / MHC class II antigen presentation / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / Neutrophil degranulation / sarcomere / endoplasmic reticulum-Golgi intermediate compartment membrane / small monomeric GTPase / secretory granule membrane / trans-Golgi network membrane / Nef mediated downregulation of MHC class I complex cell surface expression / kidney development / intracellular protein transport / cytoplasmic vesicle membrane / trans-Golgi network / cellular response to virus / positive regulation of DNA-binding transcription factor activity / peroxisome / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / protein complex oligomerization / heart development / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / postsynaptic density / early endosome / endosome / neuron projection / protein domain specific binding / lysosomal membrane / Golgi membrane / intracellular membrane-bounded organelle / innate immune response / focal adhesion / GTPase activity / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / GTP binding 類似検索 - 分子機能 AP-1 complex subunit sigma / Adaptor protein complex AP-1, gamma subunit / Gamma-adaptin ear (GAE) domain / Gamma-adaptin ear (GAE) domain profile. / ADP-ribosylation factor 1-5 / Adaptor protein complex, sigma subunit / Clathrin adaptor, beta-adaptin, appendage, Ig-like subdomain / Beta-adaptin appendage, C-terminal subdomain / AP-1/2/4 complex subunit beta / Beta2-adaptin appendage, C-terminal sub-domain ... AP-1 complex subunit sigma / Adaptor protein complex AP-1, gamma subunit / Gamma-adaptin ear (GAE) domain / Gamma-adaptin ear (GAE) domain profile. / ADP-ribosylation factor 1-5 / Adaptor protein complex, sigma subunit / Clathrin adaptor, beta-adaptin, appendage, Ig-like subdomain / Beta-adaptin appendage, C-terminal subdomain / AP-1/2/4 complex subunit beta / Beta2-adaptin appendage, C-terminal sub-domain / Beta2-adaptin appendage, C-terminal sub-domain / AP complex subunit beta / Clathrin adaptor complex, small chain / Clathrin adaptor complexes small chain signature. / Clathrin adaptor complexes medium chain signature 1. / Clathrin adaptor, mu subunit / Clathrin adaptor, mu subunit, conserved site / Clathrin adaptor complexes medium chain signature 2. / Coatomer/calthrin adaptor appendage, C-terminal subdomain / : / Stimulator of interferon genes protein / Stimulator of interferon genes protein, C-terminal domain superfamily / Transmembrane protein 173 / Adaptor complexes medium subunit family / AP complex, mu/sigma subunit / Clathrin adaptor complex small chain / AP-2 complex subunit mu, C-terminal superfamily / Mu homology domain / Mu homology domain (MHD) profile. / Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain / Adaptin C-terminal domain / Adaptin C-terminal domain / Clathrin/coatomer adaptor, adaptin-like, N-terminal / Adaptin N terminal region / small GTPase Arf family profile. / Clathrin adaptor, appendage, Ig-like subdomain superfamily / Sar1p-like members of the Ras-family of small GTPases / Small GTPase superfamily, ARF/SAR type / ADP-ribosylation factor family / Longin-like domain superfamily / ARF-like small GTPases; ARF, ADP-ribosylation factor / TBP domain superfamily / Armadillo/beta-catenin-like repeats / Armadillo / Rab subfamily of small GTPases / Armadillo-like helical / Small GTP-binding protein domain / Armadillo-type fold / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 AP-1 complex subunit gamma-1 / AP-1 complex subunit mu-1 / ADP-ribosylation factor 1 / AP-1 complex subunit beta-1 / Stimulator of interferon genes protein / AP-1 complex subunit sigma-3 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.34 Å 詳細 データ登録者Xu P / Ablasser A 資金援助 European Union, 1件 詳細 詳細を隠すOrganization Grant number 国 European Molecular Biology Organization (EMBO) ALTF-184 European Union
引用ジャーナル : Nature / 年 : 2022タイトル : Clathrin-associated AP-1 controls termination of STING signalling.著者 : Ying Liu / Pengbiao Xu / Sophie Rivara / Chong Liu / Jonathan Ricci / Xuefeng Ren / James H Hurley / Andrea Ablasser / 要旨 : Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate ... Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate immunity during infection, cancer and immunotherapy. Precise regulation of STING is essential to ensure balanced immune responses and prevent detrimental autoinflammation. After activation, STING, a transmembrane protein, traffics from the endoplasmic reticulum to the Golgi, where its phosphorylation by the protein kinase TBK1 enables signal transduction. The mechanism that ends STING signalling at the Golgi remains unknown. Here we show that adaptor protein complex 1 (AP-1) controls the termination of STING-dependent immune activation. We find that AP-1 sorts phosphorylated STING into clathrin-coated transport vesicles for delivery to the endolysosomal system, where STING is degraded. We identify a highly conserved dileucine motif in the cytosolic C-terminal tail (CTT) of STING that, together with TBK1-dependent CTT phosphorylation, dictates the AP-1 engagement of STING. A cryo-electron microscopy structure of AP-1 in complex with phosphorylated STING explains the enhanced recognition of TBK1-activated STING. We show that suppression of AP-1 exacerbates STING-induced immune responses. Our results reveal a structural mechanism of negative regulation of STING and establish that the initiation of signalling is inextricably associated with its termination to enable transient activation of immunity. 履歴 登録 2022年2月8日 - ヘッダ(付随情報) 公開 2022年9月14日 - マップ公開 2022年9月14日 - 更新 2022年11月9日 - 現状 2022年11月9日 処理サイト : PDBe / 状態 : 公開
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