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.
分子量: 28403.510 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: Residues [1-22] encode the signal peptide which is most likely removed during translation/folding. Residues [216-253] encode cloning scar, protease site, avi-tag and his-tag. Residues [224- ...詳細: Residues [1-22] encode the signal peptide which is most likely removed during translation/folding. Residues [216-253] encode cloning scar, protease site, avi-tag and his-tag. Residues [224-253] are most likely removed due to protease treatment. 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Il12a / プラスミド: pHLsec / 細胞株 (発現宿主): HEK293S MGAT1-/- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P43431