interleukin-23-mediated signaling pathway / positive regulation of T-helper 1 type immune response / positive regulation of memory T cell differentiation / interleukin-12 receptor complex / interleukin-23 receptor complex / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / interleukin-12-mediated signaling pathway / Interleukin-12 signaling / cytokine receptor activity ...interleukin-23-mediated signaling pathway / positive regulation of T-helper 1 type immune response / positive regulation of memory T cell differentiation / interleukin-12 receptor complex / interleukin-23 receptor complex / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / interleukin-12-mediated signaling pathway / Interleukin-12 signaling / cytokine receptor activity / positive regulation of activated T cell proliferation / cytokine binding / positive regulation of T-helper 17 cell lineage commitment / positive regulation of defense response to virus by host / cytokine-mediated signaling pathway / cellular response to type II interferon / positive regulation of T cell mediated cytotoxicity / positive regulation of type II interferon production / receptor complex / external side of plasma membrane / シグナル伝達 / 細胞膜 類似検索 - 分子機能
Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / フィブロネクチンIII型ドメイン / 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
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.