IL-1 Family Cytokines Use Distinct Molecular Mechanisms to Signal through Their Shared Co-receptor.
IL-1 Family Cytokines Use Distinct Molecular Mechanisms to Signal through Their Shared Co-receptor.
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DOI：
10.1016/j.immuni.2017.08.004
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发表时间：
2017-09-19
期刊：
影响因子：
32.4
通讯作者：
Sundberg EJ
中科院分区：
文献类型：
--
作者：
Günther S;Deredge D;Bowers AL;Luchini A;Bonsor DA;Beadenkopf R;Liotta L;Wintrode PL;Sundberg EJ
在白细胞介素1（IL-1）细胞因子家族中，IL-1受体辅助蛋白（IL-1 RAcP）是8种受体：细胞因子对（包括细胞因子IL-1β和IL-33）的共受体。与IL-1β不同，IL-33信号传导复合物的结构不存在既包括其同源受体ST 2又包括我们现在在这里呈现的共享共受体IL-1 RAcP。虽然IL-1β和IL-33复合物具有相同的结构特征，并与IL-1 RAcP的相同分子表面结合，但这些细胞因子具有完全不同的共受体结合和信号激活策略。我们的数据表明，IL-1β与IL-1 RI结合以将细胞因子适当地呈递给IL-1 RAcP，而IL-33与ST 2结合以在构象上将同源受体限制在IL-1 RAcP接受状态。这些发现表明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导，并为设计靶向IL-33信号传导的新疗法提供了基础。
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 cytokines IL-1β and IL-33. Unlike for IL-1β, no structure of the IL-33 signaling complex exists 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 suggested that IL-1β bound to IL-1RI to properly present the cytokine to IL-1RAcP, while IL-33 bound to ST2 in order to conformationally constrain the cognate receptor in an IL-1RAcP-receptive state. These findings indicated that IL-1 family cytokines use distinct molecular mechanisms to signal through their shared co-receptor, and provide the foundation from which to design new therapies to target IL-33 signaling.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
影响因子：
14.9
作者：
Goujon M;McWilliam H;Li W;Valentin F;Squizzato S;Paern J;Lopez R
通讯作者：
Lopez R
DOI：
10.1073/pnas.1217609110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Guan, Yongjun;Pazgier, Marzena;Lewis, George K.
通讯作者：
Lewis, George K.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
4.4
作者：
Guenther, Sebastian;Sundberg, Eric J.
通讯作者：
Sundberg, Eric J.