通过素激酶1 δ/ε对Shiftless酸化是其抗病毒活性所需的
Yongle Wang1,2, Shaozu Fu1,2, Xinlu Wang1
1State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Journal of virology
|December 2, 2025
概括
通过氨酸激酶1delta和epsilon对Shiftless (SHFL) 的酸化对于其对HIV-1的抗病毒活性至关重要. 这种翻译后的修改规范了SHFL.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 无转移 (SHFL) 是一种宿主抗病毒因子,可以抑制病毒-1编程核糖体框架转移 (-1PRF).
- 控制SHFL抗病毒活性的监管机制在很大程度上是未知的.
- 翻译后的修改,特别是酸化,对于调节先天免疫反应和抗病毒防御是至关重要的.
研究的目的:
- 阐明控制宿主因子SHFL的抗病毒活性的调控机制.
- 研究酸化在SHFL抑制病毒复制的能力中的作用,特别是HIV-1 -1PRF.
主要方法:
- 通过共免疫沉,鉴定出氨酸激酶1delta (CK1δ) 和epsilon (CK1ε) 作为SHFL相互作用的蛋白质.
- 评估了CK1δ/ε下调和药理抑制对SHFL针对HIV-1的抗病毒活性的影响.
- 利用位点定向突变生成来产生SHFL化位点突变体 (T250A,T253A),并分析了它们的抗病毒功能,RNA/蛋白相互作用和多元体关联.
主要成果:
- 通过CK1δ和CK1ε对SHFL的酸化被发现对其抗病毒活性至关重要.
- 下调或抑制CK1δ/ε显著损害了SHFL抑制HIV-1 -1PRF和病毒产生的能力.
- 在酸化位点T250和T253的突变取消了SHFL的抗病毒活性,而T250A影响了与IGF2BP蛋白质的相互作用和多元体协会.
结论:
- 通过CK1δ/ε对SHFL的酸化是其针对HIV-1的抗病毒功能所需的关键调节机制.
- 通过酸化调节的SHFL与核糖体的相互作用对其对1PRF的抑制活性至关重要.
- 这些发现提供了对先天免疫反应调节的见解,并为研究1PRF机制提供了工具.
相关概念视频
Protein Kinases and Phosphatases
14.9K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
14.9K
Protein Kinases and Phosphatases
4.3K
4.3K
Phosphorylation
53.5K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
53.5K
Anaphase Promoting Complex
3.3K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.3K
The JAK-STAT Signaling Pathway
11.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.8K
cAMP-dependent Protein Kinase Pathways
8.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.2K


