登録情報 データベース : EMDB / ID : EMD-26382 ダウンロードとリンクタイトル IL-27 quaternary receptor signaling complex マップデータSharpened Map 詳細 試料複合体 : IL-27 quaternary receptor signaling complexタンパク質・ペプチド : Interleukin-27 receptor subunit alphaタンパク質・ペプチド : Interleukin-6 receptor subunit betaタンパク質・ペプチド : Interleukin-27 subunit betaタンパク質・ペプチド : Interleukin-27 subunit alphaリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 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
interleukin-27 receptor binding / regulation of T-helper 1 cell differentiation / negative regulation of T cell extravasation / negative regulation of T-helper 17 type immune response / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / leukemia inhibitory factor signaling pathway / negative regulation of type 2 immune response / negative regulation of interleukin-6-mediated signaling pathway ... interleukin-27 receptor binding / regulation of T-helper 1 cell differentiation / negative regulation of T cell extravasation / negative regulation of T-helper 17 type immune response / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / leukemia inhibitory factor signaling pathway / negative regulation of type 2 immune response / negative regulation of interleukin-6-mediated signaling pathway / oncostatin-M receptor complex / regulation of isotype switching to IgG isotypes / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor-mediated signaling pathway / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / interleukin-6 receptor complex / response to Gram-positive bacterium / interleukin-11-mediated signaling pathway / positive regulation of T-helper 1 type immune response / T-helper 17 cell lineage commitment / positive regulation of alpha-beta T cell proliferation / positive regulation of adaptive immune response / positive regulation of acute inflammatory response / positive regulation of astrocyte differentiation / intestinal epithelial cell development / positive regulation of platelet aggregation / negative regulation of interleukin-17 production / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / cytokine receptor activity / T-helper 1 type immune response / glycogen metabolic process / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / positive regulation of Notch signaling pathway / regulation of T cell proliferation / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / MAPK3 (ERK1) activation / cytokine binding / growth factor binding / MAPK1 (ERK2) activation / negative regulation of interleukin-6 production / humoral immune response / negative regulation of tumor necrosis factor production / positive regulation of vascular endothelial growth factor production / positive regulation of osteoblast differentiation / positive regulation of defense response to virus by host / coreceptor activity / positive regulation of T cell proliferation / T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / response to cytokine / cytokine activity / cytokine-mediated signaling pathway / positive regulation of type II interferon production / transmembrane signaling receptor activity / scaffold protein binding / negative regulation of neuron apoptotic process / receptor complex / cell surface receptor signaling pathway / defense response to Gram-positive bacterium / inflammatory response / immune response / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / innate immune response / signaling receptor binding / neuronal cell body / positive regulation of cell population proliferation / dendrite / negative regulation of apoptotic process / cell surface / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol 類似検索 - 分子機能 Interleukin-27 alpha / : / : / Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, Gp130 family 2, conserved site ... Interleukin-27 alpha / : / : / Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / : / Four-helical cytokine-like, core / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Interleukin-6 receptor subunit beta / Interleukin-27 subunit beta / Interleukin-27 receptor subunit alpha / Interleukin-27 subunit alpha 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.47 Å 詳細 データ登録者Caveney NA / Glassman CR / Jude KM / Tsutsumi N / Garcia KC 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) R01-AI51321 米国
引用ジャーナル : Elife / 年 : 2022タイトル : Structure of the IL-27 quaternary receptor signaling complex.著者 : Nathanael A Caveney / Caleb R Glassman / Kevin M Jude / Naotaka Tsutsumi / K Christopher Garcia / 要旨 : Interleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface ... Interleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface receptors, IL-27Rα and gp130, results in activation of receptor-associated Janus Kinases and nuclear translocation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3 transcription factors. Despite the emerging therapeutic importance of this cytokine axis in cancer and autoimmunity, a molecular blueprint of the IL-27 receptor signaling complex, and its relation to other gp130/IL-12 family cytokines, is currently unclear. We used cryogenic-electron microscopy to determine the quaternary structure of IL-27, composed of p28 and Epstein-Barr Virus-Induced 3 (Ebi3) subunits, bound to receptors, IL-27Rα and gp130. The resulting 3.47 Å resolution structure revealed a three-site assembly mechanism nucleated by the central p28 subunit of the cytokine. The overall topology and molecular details of this binding are reminiscent of IL-6 but distinct from related heterodimeric cytokines IL-12 and IL-23. These results indicate distinct receptor assembly mechanisms used by heterodimeric cytokines with important consequences for targeted agonism and antagonism of IL-27 signaling. 履歴 登録 2022年3月7日 - ヘッダ(付随情報) 公開 2022年5月25日 - マップ公開 2022年5月25日 - 更新 2022年5月25日 - 現状 2022年5月25日 処理サイト : RCSB / 状態 : 公開
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