影响人类的H1N1菌株RNA依赖RNA聚合酶的结构动力学:一种生物信息学方法
Mahesh Samantaray1, Shilpa Sri Pushan1, Muthukumaran Rajagopalan2
1Department of Bioinformatics, School of Life Sciences, Pondicherry University, R. V. Nagar, Puducherry, India.
Journal of biomolecular structure & dynamics
|September 20, 2023
概括
这项研究表明,H1N1RNA依赖RNA聚合酶 (RdRp) 突变增强了结构稳定性和灵活性. 这些发现为流感病毒动态和潜在的抑制剂开发提供了洞察力.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 由于通过空气传播,流感流感对社会构成重大风险.
- H1N1菌株,特别是在2009年大流行之后,一直是计算研究的焦点.
- 依赖RNA的RNA聚合酶 (RdRp) 复合体对于H1N1病毒中的病毒RNA合成至关重要.
研究的目的:
- 为了研究H1N1RNA依赖RNA聚合酶 (RdRp) 复合物的结构动力学.
- 分析17种特定突变对RdRp结构和稳定性的影响.
- 了解不同RdRp域之间的相互作用及其在病毒RNA结合中的作用.
主要方法:
- 对H1N1 RdRp复合物的计算分析.
- 检查野生类型和突变菌株的结构动态和残留-残留相互作用.
- 对域移动的分析,包括PA内核酶,PB1RNA入口区域和PB2封锁结合区域.
主要成果:
- 突变H1N1 RdRp菌株通过协同的单体内和单体间相互作用表现出增强的稳定性.
- 突变菌株表现出增加的结构灵活性与稳定相互作用相结合.
- 控制RdRp动态的关键域包括PA内核酶,PB1RNA入口区域和PB2封锁结合区域.
- PB2封锁结合区域与PB1RNA输入区域显示协调的运动,以及与PA内核酶域的抗相关运动,支持稳定的RNA结合.
结论:
- 这项研究阐明了大流行和突变H1N1 RdRp的结构动态.
- 这些发现强调了特定突变和域相互作用的稳定作用.
- 这项研究为开发新型流感抑制剂提供了基础知识.
相关概念视频
Leaky Scanning
5.2K
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...
5.2K
Bacterial RNA Polymerase
29.6K
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
29.6K
Viral Mutations
32.4K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.4K
Viruses with RNA Genomes
55
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
55
Eukaryotic RNA Polymerases
24.3K
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
24.3K
Transcription Initiation
16.5K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.5K


