Structure and functional characterization of the RNA-binding element of the NLRX1 innate immune modulator.

Structure and functional characterization of the RNA-binding element of the NLRX1 innate immune modulator.
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DOI:
10.1016/j.immuni.2011.12.018
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发表时间:
2012-03-23
期刊:
影响因子:
32.4
通讯作者:
Wilson IA
Wilson IA
中科院分区:
医学1区
文献类型:
--
作者:
Hong M;Yoon SI;Wilson IA

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线粒体NLRX1是核苷酸结合域和富含亮氨酸重复序列的蛋白家族的一员,作为细胞内对常见入侵病原体分子模式的监视感受器,介导宿主的天然免疫。NLRX1在抗病毒免疫中发挥作用,但其配体诱导激活的分子机制很大程度上尚不清楚。人NLRX1(CNLRX1)C-末端片段(残基629-975)的晶体结构表明,cNLRX1由N-末端螺旋(LRRNT)结构域、中心富含亮氨酸的重复模块(LRRM)和C-末端三螺旋束(LRRCT)组成。CNLRX1组装成一个紧凑的六聚体结构,该结构分别由六聚体的三聚体和二聚体中的LRRNT和LRRCT的亚基间和结构域间的相互作用稳定。此外,我们发现cNLRX1直接与RNA相互作用,并支持NLRX1在抗病毒免疫中识别细胞内病毒RNA的作用。
Mitochondrial NLRX1 is a member of the family of nucleotide-binding domain and leucine-rich-repeat–containing proteins (NLRs) that mediate host innate immunity as intracellular surveillance sensors against common molecular patterns of invading pathogens. NLRX1 functions in antiviral immunity, but the molecular mechanism of its ligand-induced activation is largely unknown. The crystal structure of the C-terminal fragment (residues 629-975) of human NLRX1 (cNLRX1) at 2.65 Å resolution reveals that cNLRX1 consists of an N-terminal helical (LRRNT) domain, central leucine-rich repeat modules (LRRM) and a C-terminal three-helix bundle (LRRCT). cNLRX1 assembles into a compact hexameric architecture that is stabilized by inter-subunit and inter-domain interactions of LRRNT and LRRCT in the trimer and dimer components of the hexamer, respectively. Furthermore, we find that cNLRX1 interacts directly with RNA and supports a role for NLRX1 in recognition of intracellular viral RNA in antiviral immunity.
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