麻疹病毒三元聚合酶复合物的结构
Dong Wang1, Ge Yang1, Bin Liu2
1Section of Transcription & Gene Regulation, The Hormel Institute, University of Minnesota, Austin, MN, USA.
Nature communications
|April 23, 2025
概括
麻疹病毒 (MeV) 聚合酶结构揭示了病毒复制的关键相互作用. 这些发现为开发针对这种传染性病原体的抗病毒疗法提供了新的目标.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 麻疹病毒 (MeV) 是一种高度传染性的病原体,导致全球显著的发病率.
- MeV聚合酶复合体 (L和P蛋白) 对于病毒复制和转录至关重要.
- 这个复合体是抗病毒药物开发的有希望的目标.
研究的目的:
- 确定两个不同的MeV聚合酶复合物的冷电子显微镜结构:Lcore-P和Lfull-P-C.
- 阐明这些复杂物体内的分子结构和相互作用.
- 为了确定抗病毒治疗的潜在干预目标.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 解析了MeV聚合酶复合物的结构.
- 对Lcore-P复合物的分析,包括RNA依赖的RNA聚合酶 (RdRp) 和L的GDP多核核酸转移酶域,以及四重性P的分析.
- 对Lfull-P-C复合物的分析,详细说明C蛋白二次体的结合.
主要成果:
- Lcore-P结构描述了MeV聚合酶的核心组成部分.
- Lfull-P-C结构显示了C蛋白二聚体结合,可视化了灵活的L蛋白域 (连接,甲基转移酶,C终端).
- 这种相互作用创建了一个扩展的RNA通道,可能调节RNA合成和退出.
结论:
- 该研究提供了MeV聚合酶复合物的高分辨率结构,详细说明了它们的架构.
- 这些结构为MeV复制机制提供了新的见解.
- 这些发现确定了针对麻疹病毒的新型抗病毒策略的潜在目标.
相关概念视频
02:41Protein Complex Assembly
10.4K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.4K
03:01The Replisome
32.5K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
32.5K
02:10Translesion DNA Polymerases
9.7K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
9.7K
00:43Bacterial RNA Polymerase
8.3K
8.3K
00:58Eukaryotic RNA Polymerases
5.3K
5.3K
02:28Leaky Scanning
5.0K
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...
5.0K