埃博拉病毒VP35与无素链相互作用,以促进病毒复制
Carlos A Rodríguez-Salazar1,2, Sarah van Tol1, Olivier Mailhot3
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS biology
|February 29, 2024
概括
埃博拉病毒 (EBOV) VP35蛋白与乌比奎丁链相互作用,影响病毒复制. 研究人员发现了针对这种相互作用的化合物,可以减少细胞和小鼠中的EBOV复制.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 埃博拉病毒 (EBOV) 引起严重的出血热.
- 病毒聚合酶复合体,包括VP35辅因子,对于EBOV复制至关重要.
- VP35的共价泛基化调节了聚合酶相互作用,但其非共价泛基结合功能尚不清楚.
研究的目的:
- 为了研究VP35与ubiquitin的非共价相互作用的功能.
- 识别针对EBOV的潜在治疗点和化合物.
主要方法:
- 研究了VP35与自由K63结合的多比基链的相互作用.
- 利用异酶T (USP5) 来评估未定聚基因链的作用.
- 使用计算建模来识别VP35-ubiquitin交互界面.
- 使用对接模拟对阻断VP35-ubiquitin相互作用的化合物进行选.
- 在基于细胞的测定和小鼠模型中评估化合物的疗效.
主要成果:
- VP35与自由的K63结合的多比基链进行非共价相互作用.
- USP5表达减少了VP35-ubiquitin关联和病毒聚合酶活性.
- 计算机建模确定了VP35-ubiquitin相互作用接口.
- 已确定阻断VP35-ubiquitin相互作用的化合物,降低聚合酶活性.
- 这些化合物在体外和体内表现出抗EBOV活性.
结论:
- 无聚比基因在调节EBOV聚合酶功能的过程中发挥了新的作用.
- 针对VP35-ubiquitin相互作用为EBOV治疗提供了一个有前途的战略.
- 已识别的化合物显示出作为抗埃博拉病毒代理物的潜力.
相关概念视频
Intralumenal Vesicles and Multivesicular Bodies
3.5K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.5K
Leaky Scanning
5.1K
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...
5.1K
Receptor-mediated Endocytosis
6.1K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
6.1K
Retroviruses
12.3K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.3K


