Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly,FEBS Letters

当前位置： X-MOL 学术 › FEBS Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly
FEBS Letters ( IF 3.0 ) Pub Date : 2020-07-06 , DOI: 10.1002/1873-3468.13865
Michael Marleaux ₁ , Kanchan Anand ₁ , Eicke Latz ₂ , Matthias Geyer ₁

Affiliation

Inflammasomes are cytosolic multimeric signaling complexes of the innate immune system that induce activation of caspases. The NOD-like receptor NLRP9 recruits the adaptor protein ASC to form an ASC-dependent inflammasome to limit rotaviral replication in intestinal epithelial cells, but only little is known about the molecular mechanisms regulating and driving its assembly. Here, we present the crystal structure of the human NLRP9 pyrin domain. We show that NLRP9PYD is not able to self-polymerize nor to nucleate ASC specks in HEK293T cells. Comparison with filament forming pyrin domains revealed that NLRP9PYD adopts a conformation compatible with filament formation but several charge inversions of interfacing residues might cause repulsive effects that prohibit self-oligomerization. These results propose that inflammasome assembly of NLRP9 might differ largely from what we know of other inflammasomes.

中文翻译：

人 NLRP9 pyrin 结构域的晶体结构表明炎性体组装的独特模式

炎性体是先天免疫系统的胞质多聚体信号复合物，可诱导半胱天冬酶的激活。NOD 样受体 NLRP9 募集接头蛋白 ASC 形成 ASC 依赖性炎症小体，以限制肠上皮细胞中的轮状病毒复制，但对调节和驱动其组装的分子机制知之甚少。在这里，我们展示了人 NLRP9 pyrin 结构域的晶体结构。我们表明 NLRP9PYD 不能自聚合，也不能使 HEK293T 细胞中的 ASC 斑点成核。与形成细丝的 pyrin 结构域的比较表明，NLRP9PYD 采用与细丝形成相容的构象，但界面残基的几种电荷反转可能会导致排斥效应，从而阻止自低聚化。

更新日期：2020-07-06

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11