Crystal structure of IL-17 receptor B SEFIR domain.
Crystal structure of IL-17 receptor B SEFIR domain.
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DOI：
10.4049/jimmunol.1202922
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Deng J
中科院分区：
文献类型：
--
作者：
Zhang B;Liu C;Qian W;Han Y;Li X;Deng J
白细胞介素17 （IL-17）细胞因子在多种炎症和自身免疫性疾病中起着至关重要的作用。它们通过由IL-17受体（IL-17R）家族成员组成的异二聚体受体复合物发出信号。在所有IL-17Rs中发现了一个独特的细胞内信号域，称为SEFIR [SEF（与成纤维细胞生长因子基因相似的表达）和IL-17R]。SEFIR也存在于E3泛素连接酶核因子κB （NF-κB）激活因子1 （Act1）中，并介导其向IL-17Rs的募集。在这里，我们以1.8Å分辨率报道了IL-17RB的第一个SEFIR结构域的结构。SEFIR显示了由六个螺旋包裹的五股平行β片。对IL-17RB进行定点诱变，发现螺旋αC在其与Act1和IL-25 （IL-17E）信号相互作用中起关键作用。以当前SEFIR结构为模板，Act1中的关键功能残基也被定位为αC螺旋的一部分，αC在IL-17RA和RC中保守，表明该螺旋是SEFIR- serir异型关联的共同结构特征。另一方面，螺旋αB′对于Act1的同型二聚化很重要，这暗示了SEFIR结构域的双配体结合模式，不同的结构基序参与同型或异型相互作用。此外，尽管IL-17RB-SEFIR结构与TLR10的Toll/Interleukin-1受体（TIR）结构域最相似，序列同源性较低，但在螺旋αC、αD和DD '环上观察到显著差异。本研究提供了IL-17受体细胞内信号传导的第一个结构视图，揭示了SEFIR与TIR结构域在各自信号通路中的特异性机制。
Interleukin 17 (IL-17) cytokines play a crucial role in a variety of inflammatory and autoimmune diseases. They signal through heterodimeric receptor complexes consisting of members of IL-17 receptor (IL-17R) family. A unique intracellular signaling domain was identified within all IL-17Rs, termed SEFIR [SEF (similar expression to fibroblast growth factor genes) and IL-17R]. SEFIR is also found in nuclear factor κB (NF-κB) activator 1 (Act1), an E3 ubiquitin ligase, and mediates its recruitment to IL-17Rs. Here we report the structure of the first SEFIR domain from IL-17RB at 1.8Å resolution. SEFIR displays a five-stranded parallel β-sheet that is wrapped by six helices. Site-directed mutagenesis on IL-17RB identified helix αC as being critical for its interaction with Act1 and IL-25 (IL-17E) signaling. Using the current SEFIR structure as a template, the key functional residues in Act1 are also mapped as part of helix αC, which is conserved in IL-17RA and RC, suggesting this helix as a common structural signature for heterotypic SEFIR-SERIR association. On the other hand, helix αB′ is important for homo-dimerization of Act1, implicating a dual ligand-binding model for SEFIR domain, with distinct structural motifs participating in either homotypic or heterotypic interactions. Furthermore, although IL-17RB-SEFIR structure resembles closest to the Toll/Interleukin-1 receptor (TIR) domain of TLR10 with low sequence homology, substantial differences were observed at helices αC, αD and DD′ loop. This study provides the first structural view of the IL-17 receptor intracellular signaling, unraveling the mechanism for the specificity of SEFIR versus TIR domain in their respective signaling pathways.
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影响因子：
2.9
作者：
Lee, Julian;Lee, Dongseon;Park, Hahnbeom;Coutsias, Evangelos A.;Seok, Chaok
通讯作者：
Seok, Chaok
DOI：
10.4049/jimmunol.182.3.1631
发表时间：
2009-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Siebenlist, Ulrich
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7.3
作者：
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Li X