登録情報 データベース : EMDB / ID : EMD-16823 ダウンロードとリンクタイトル Cryo-EM structure of the murine IL-12 complete extracellular signaling complex (Class 2). マップデータSharpened map of the murine IL12:IL12Rbeta1:IL12Rbeta2 complex (Class 2). 詳細 試料複合体 : Murine IL-12 in complex with Strep-II tagged mIL-12Rbeta1 and mIL-12Rbeta2.タンパク質・ペプチド : Murine Interleukin-12 subunit alpha (IL-12A, p35), with a C-terminal caspase-3 cleavable His tag.タンパク質・ペプチド : Murine Interleukin-12 subunit beta (IL-12B, p40).タンパク質・ペプチド : Murine Interleukin-12 Receptor beta 1 (domains 1 to 5) with C-terminal Strep-II tag.タンパク質・ペプチド : Murine Interleukin-12 Receptor beta 2 (domains 1 to 6) with C-terminal Strep-II tag. 詳細 キーワード Complex / Cytokine / Receptor / SIGNALING PROTEIN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-12 beta subunit binding / Interleukin-12 signaling / Interleukin-23 signaling / interleukin-23 receptor binding / Interleukin-35 Signalling / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / T-helper 1 cell activation / natural killer cell activation involved in immune response ... interleukin-12 beta subunit binding / Interleukin-12 signaling / Interleukin-23 signaling / interleukin-23 receptor binding / Interleukin-35 Signalling / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / T-helper 1 cell activation / natural killer cell activation involved in immune response / positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of vascular endothelial growth factor signaling pathway / negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis / positive regulation of T-helper 1 type immune response / positive regulation of smooth muscle cell apoptotic process / interleukin-12 receptor binding / natural killer cell activation / T-helper cell differentiation / interleukin-23 receptor complex / positive regulation of osteoclast differentiation / negative regulation of interleukin-17 production / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / response to UV-B / positive regulation of granulocyte macrophage colony-stimulating factor production / positive regulation of natural killer cell proliferation / positive regulation of T cell differentiation / cytokine receptor activity / negative regulation of interleukin-10 production / cytokine binding / positive regulation of activated T cell proliferation / defense response to protozoan / positive regulation of interleukin-17 production / positive regulation of interleukin-10 production / immunoglobulin mediated immune response / negative regulation of protein secretion / coreceptor activity / T cell proliferation / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / negative regulation of inflammatory response to antigenic stimulus / positive regulation of defense response to virus by host / positive regulation of interleukin-12 production / : / response to cytokine / cytokine activity / endosome lumen / negative regulation of smooth muscle cell proliferation / growth factor activity / cytokine-mediated signaling pathway / cellular response to type II interferon / Golgi lumen / positive regulation of T cell mediated cytotoxicity / positive regulation of tumor necrosis factor production / positive regulation of type II interferon production / cell migration / cellular response to lipopolysaccharide / defense response to virus / defense response to Gram-negative bacterium / cell population proliferation / response to lipopolysaccharide / cell surface receptor signaling pathway / receptor complex / immune response / protein heterodimerization activity / endoplasmic reticulum lumen / external side of plasma membrane / protein-containing complex binding / protein kinase binding / cell surface / extracellular space / extracellular region / identical protein binding / plasma membrane / cytoplasm 類似検索 - 分子機能 Interleukin-12 alpha / Interleukin-12 alpha subunit / Interleukin-12 beta / Interleukin-12 beta, central domain / Cytokine interleukin-12p40 C-terminus / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Long hematopoietin receptor, Gp130 family 2, conserved site ... Interleukin-12 alpha / Interleukin-12 alpha subunit / Interleukin-12 beta / Interleukin-12 beta, central domain / Cytokine interleukin-12p40 C-terminus / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / 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 / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Interleukin-12 subunit alpha / Interleukin-12 subunit beta / Interleukin-12 receptor subunit beta-2 / Interleukin-12 receptor subunit beta-1 類似検索 - 構成要素生物種 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 : 6.7 Å 詳細 データ登録者Felix J / Bloch Y / Savvides SN 資金援助 ベルギー, 2件 詳細 詳細を隠すOrganization Grant number 国 Research Foundation - Flanders (FWO) 12S0519N ベルギー Research Foundation - Flanders (FWO) G0B4918N ベルギー
引用ジャーナル : Nat Struct Mol Biol / 年 : 2024タイトル : Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23.著者 : Yehudi Bloch / Jan Felix / Romain Merceron / Mathias Provost / Royan Alipour Symakani / Robin De Backer / Elisabeth Lambert / Ahmad R Mehdipour / Savvas N Savvides / 要旨 : Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into ... Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12-receptor interaction interfaces, in contrast to IL-23-receptor complexes. Here we report structures of fully assembled mouse IL-12/human IL-23-receptor complexes comprising the complete extracellular segments of the cognate receptors determined by electron cryo-microscopy. The structures reveal key commonalities but also surprisingly diverse features. Most notably, whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig domain of their high-affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell membrane. Collectively, our findings will help to complete our understanding of cytokine-mediated assemblies of tall cytokine receptors and will enable a cytokine-specific interrogation of IL-12/IL-23 signaling in physiology and disease. 履歴 登録 2023年3月10日 - ヘッダ(付随情報) 公開 2024年2月7日 - マップ公開 2024年2月7日 - 更新 2024年5月1日 - 現状 2024年5月1日 処理サイト : PDBe / 状態 : 公開
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