冠状病毒主要蛋白酶诱导LPCAT3裂变和内质网膜 (ER) 压力
Jia Wang1, Meifang Zhang1,2, Yanli Ding1
1Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Viruses
|August 26, 2023
概括
冠状病毒通过分裂LPCAT3,这是一种对脂质吸收至关重要的酶,导致胃肠道问题. 这种裂变可能导致COVID-19等感染期间的吸收不良和腹.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
背景情况:
- 动物性冠状病毒在哺乳动物和鸟类中引起肺部和胃肠道感染.
- 严重的腹和死亡与PEDV和TGEV等动物冠状病毒有关.
- 胃肠道症状在人类冠状病毒疾病如COVID-19和SARS中观察到,但它们的发病因子尚不清楚.
研究的目的:
- 为了调查冠状病毒感染中胃肠道症状背后的机制.
- 探索主要蛋白酶 (Mpro) 在冠状病毒引起的胃肠道病理中的作用.
- 为了确定Mpro,LPCAT3和内质网膜 (ER) 应激之间的关系.
主要方法:
- 外源基因表达和蛋白酶抑制剂被用于监测Mpro诱导的LPCAT3裂变.
- 定量逆转录PCR (qRT-PCR) 和基因淘汰证实了基因表达的调节.
- 突变酶分析和抑制剂实验评估了催化活性在LPCAT3裂变中的作用.
主要成果:
- LPCAT3裂变是由导致腹的冠状病毒 (PEDV,MERS-CoV) 的Mpro诱导的,而不是其他冠状病毒 (HCoV-OC43,HCoV-HKU1).
- LPCAT3裂变独立于Mpro的催化活性.
- 在LPCAT3裂隙中,CHOP和GRP78的表达升高,表明ER应力.
结论:
- LPCAT3对于肠道脂质吸收至关重要.
- 在冠状病毒感染期间,Mpro诱导的LPCAT3裂变可能会通过吸收不良和ER压力引发胃肠道症状.
相关概念视频
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Tail-anchoring of Proteins in the ER Membrane
3.1K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K
Role of ER in the Secretory Pathway
5.5K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.5K
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Directing Proteins to the Rough Endoplasmic Reticulum
7.3K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.3K


