在疟疾中通过RIFIN激活LILRB1的结构基础
Thomas E Harrison1, Alexander M Mørch1,2, James H Felce2
1Department of Biochemistry, University of Oxford, Oxford, UK.
Nature
|July 11, 2020
概括
导致疟疾的Plasmodium falciparum使用RIFIN蛋白来结合免疫受体LILRB1,模仿自然连接体并抑制自然杀手 (NK) 细胞功能.
科学领域:
- 免疫学
- 寄生虫学
- 结构生物学
背景情况:
- 疟疾寄生虫,特别是Plasmodium falciparum,在感染的红细胞上显示RIFIN蛋白质.
- 一些RIFIN与LILRB1等免疫受体相互作用,可能抑制宿主免疫反应.
- 了解RIFIN-LILRB1的相互作用对于了解疟疾免疫规避至关重要.
研究的目的:
- 阐明LILRB1介导信号的RIFIN激活的结构基础.
- 研究RIFINs如何模仿自然连接体并影响免疫细胞功能.
主要方法:
- 确定与LILRB1结合的RIFIN的晶体结构.
- 使用突变分析来评估RIFIN-LILRB1复杂干扰和信号.
- 采用支持的脂质双层系统来模拟NK细胞激活和测量免疫细胞反应.
主要成果:
- 结构显示RIFIN在LILRB1结合模式中模仿MHC I类.
- 一个RIFIN突变取消了LILRB1的结合和下游信号.
- 与MHC一样,RIFIN被招募到NK细胞免疫突触中,减少NK细胞的激活和穿孔素的调动.
结论:
- RIFINs使用类似于自然LILRB1配体的结合模式来抑制NK细胞功能.
- 这种模仿代表了Plasmodium falciparum的新型免疫规避策略.
- 向RIFIN-LILRB1相互作用可能为抗疟疾提供新的治疗途径.
更多相关视频
09:13Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
1.7K
12:43Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
12.6K
相关概念视频
01:07MAPK Signaling Cascades
7.6K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.6K
01:23Transcriptional Regulation: Riboswitches
399
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
399
02:28Leaky Scanning
5.5K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.5K