基于Lamassu的抗病毒免疫的结构基础及其从DNA修复机械的演变
bioRxiv : the preprint server for biology
|April 16, 2025
概括
细菌免疫系统Lamassu使用一种改性DNA修复蛋白来检测病毒DNA并触发抗菌体反应. 这项研究揭示了它的结构和进化起源,来自现有的细胞机械.
科学领域:
- 细菌学 细菌学是一门学科.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 细菌抗菌体免疫表现出多样性和模块性,这是由于菌体掠食.
- 抗菌体系统的进化起源,特别是那些涉及SMC蛋白质的抗菌体系统,尚不清楚.
研究的目的:
- 阐明拉马苏细菌免疫系统的结构基础和进化性出现.
- 了解Lamassu如何感知病毒DNA并激活下游效应器.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定拉马苏复合体的结构.
- 在体外DNA结合测试以评估dsDNA传感.
- 在体内实验以调查菌体复制原始识别.
主要成果:
- 确定了Vibrio cholerae Lamassu复合体在apo和dsDNA结合状态中的冷EM结构,揭示了新的架构.
- 通过Lamassu证明了dsDNA和菌体复制起源的特定感知.
- 显示Lamassu触发了LmuA四分体的形成和Cap4核酶的激活.
结论:
- 拉马苏通过Rad50-Mre11 DNA修复系统的捕获而进化.
- 它作为一个紧的模块化传感器,用于病毒复制,并采用细胞机械来进行免疫防御.
相关概念视频
Translesion 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
Viral Mutations
32.0K
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...
32.0K
The Replisome
32.6K
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...
32.6K
Overview of DNA Repair
29.4K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
29.4K
Mismatch Repair
4.7K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.7K
Homologous Recombination
49.8K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
49.8K


