Structural insights into heme binding to IL-36α proinflammatory cytokine
Structural insights into heme binding to IL-36α proinflammatory cytokine
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DOI：
10.1038/s41598-019-53231-0
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发表时间：
2019-11-15
影响因子：
4.6
通讯作者：
Imhof, Diana
中科院分区：
文献类型：
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作者：
Wissbrock, Amelie;Goradia, Nishit B.;Imhof, Diana
白细胞介素（IL）-1家族的细胞因子调节免疫和炎症反应。最近发现的IL-36家族成员与银屑病、类风湿性关节炎和肺部疾病有关。在这里，我们表明IL-36 α与血红素相互作用，从而有助于其调节。基于深入的光谱分析，我们描述了IL-36 α中的两个血红素结合位点，它们以五配位的方式与血红素结合。溶液NMR分析揭示了IL-36 α及其与血红素的复合物的结构特征。截短的IL-36 α的结构研究支持N-末端对于与其同源受体结合是必需的这一观点。与我们的结构研究一致，IL-36介导的信号转导在类风湿性关节炎患者的滑膜成纤维细胞样滑膜细胞中受到血红素的负调控。两者合计，我们的研究结果提供了一个血红素结合蛋白的结构框架，并添加IL-1细胞因子的潜在血红素调节蛋白质组。
Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36 alpha interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36 alpha that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36 alpha and its complex with heme. Structural investigation of a truncated IL-36 alpha supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.