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IL-1 Family Cytokines Use Distinct Molecular Mechanisms to Signal through Their Shared Co-receptor
Immunity ( IF 25.5 ) Pub Date : 2017-09-19 , DOI: 10.1016/j.immuni.2017.08.004
Sebastian Günther , Daniel Deredge , Amanda L. Bowers , Alessandra Luchini , Daniel A. Bonsor , Robert Beadenkopf , Lance Liotta , Patrick L. Wintrode , Eric J. Sundberg

Within the interleukin 1 (IL-1) cytokine family, IL-1 receptor accessory protein (IL-1RAcP) is the co-receptor for eight receptor-cytokine pairs, including those involving cytokines IL-1β and IL-33. Unlike IL-1β, IL-33 does not have a signaling complex that includes both its cognate receptor, ST2, and the shared co-receptor IL-1RAcP, which we now present here. Although the IL-1β and IL-33 complexes shared structural features and engaged identical molecular surfaces of IL-1RAcP, these cytokines had starkly different strategies for co-receptor engagement and signal activation. Our data suggest that IL-1β binds to IL-1RI to properly present the cytokine to IL-1RAcP, whereas IL-33 binds to ST2 in order to conformationally constrain the cognate receptor in an IL-1RAcP-receptive state. These findings indicate that members of the IL-1 family of cytokines use distinct molecular mechanisms to signal through their shared co-receptor, and they provide the foundation from which to design new therapies to target IL-33 signaling.



中文翻译:

IL-1家族细胞因子使用不同的分子机制通过其共享的共受体进行信号传递

在白介素1(IL-1)细胞因子家族中,IL-1受体辅助蛋白(IL-1RAcP)是八种受体-细胞因子对的共受体,包括那些涉及细胞因子IL-1β和IL-33的受体。与IL-1β不同,IL-33没有包含其同源受体ST2和共享的共受体IL-1RAcP的信号传导复合物,我们现在在此进行介绍。尽管IL-1β和IL-33复合物具有相同的结构特征并与IL-1RAcP的分子表面结合,但这些细胞因子对于共受体结合和信号激活具有截然不同的策略。我们的数据表明,IL-1β与IL-1RI结合以正确地将细胞因子呈递给IL-1RAcP,而IL-33与ST2结合,以构象地限制同源受体处于IL-1RAcP接受状态。

更新日期:2017-09-19
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