受体
细胞外
细胞生物学
细胞因子受体
白细胞介素23
细胞表面受体
白细胞介素-4受体
蛋白质亚单位
白细胞介素5受体α亚单位
信号转导
生物
细胞因子
化学
白细胞介素
白细胞介素-21受体
Gα亚单位
生物化学
免疫学
基因
作者
Yehudi Bloch,Jan Félix,Romain Merceron,Mathias Provost,Royan Alipour Symakani,Robin De Backer,Elisabeth Lambert,Savvas N. Savvides
标识
DOI:10.1101/2023.03.13.532366
摘要
Abstract Cell-surface receptor complexes mediated by pro-inflammatory Interleukin-12 and -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 IL23:receptor complexes. Here we report cryo-EM structures of fully assembled IL-12/IL-23:receptor complexes comprising the complete extracellular segments of the cognate receptors. The structures reveal important commonalities but also surprisingly diverse features. 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 enable a cytokine-specific interrogation of IL-12 and IL-23 signaling in physiology and disease.
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