Crystal structure of the human NLRP9 pyrin domain reveals a bent N-terminal loop that may regulate inflammasome assembly
Crystal structure of the human NLRP9 pyrin domain reveals a bent N-terminal loop that may regulate inflammasome assembly
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DOI：
10.1002/1873-3468.13866
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发表时间：
2020-06-28
期刊：
影响因子：
3.5
通讯作者：
Park, Hyun Ho
中科院分区：
文献类型：
--
作者：
Ha, Hyun Ji;Park, Hyun Ho
含有热蛋白结构域的 NLR 家族 (NLRP) 的成员是参与先天免疫的模式识别受体。它们形成炎症小体，这是 caspase-1 招募和激活的平台。 NLRP 吡啶结构域 (PYD) 由于其介导蛋白质相互作用的能力，对于炎症小体的组装至关重要。尽管对带有 PYD 的炎症小体进行了深入的结构研究，但 NLRP9（该家族中研究最少的成员）的 PYD 结构仍然未知。在此，我们以 2.1 埃分辨率报告了人类 NLRP9 PYD 的晶体结构，其揭示了一个朝向螺旋束内部的扭结 N 端环。根据我们的发现，我们提出 NLRP9 PYD 的 N 末端扭结环在炎症小体组装中的调节作用。
Members of the NLR family pyrin domain containing (NLRPs) are pattern recognition receptors that participate in innate immunity. They form inflammasomes, which are platforms for caspase-1 recruitment and activation. The NLRP pyrin domain (PYD) is critical for the assembly of inflammasomes due to its ability to mediate protein interactions. Despite intensive structural studies on inflammasomes with PYDs, the structure of the PYD of NLRP9-the least studied member of the family-remains unknown. Herein, we report the crystal structure of the human NLRP9 PYD at 2.1 angstrom resolution, which reveals a kinked N-terminal loop oriented toward the interior of the helical bundle. Based on our findings, we propose a regulatory role for the kinked N-terminal loop of NLRP9 PYD in inflammasome assembly.