一个α螺旋盖将目标DNA引导到CRISPR-Cas12a中的催化过程中
Aakash Saha1, Mohd Ahsan1, Pablo R Arantes1
1Department of Bioengineering, University of California Riverside, 900 University Avenue, Riverside, CA, 52512, USA.
Nature communications
|February 17, 2024
概括
基因组编辑系统CRISPR-Cas12a使用一种独特的机制来切割DNA. 分子模拟显示,一个α-螺旋盖引导DNA向RuvC核心进行编辑.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 基因组学就是基因组学.
背景情况:
- CRISPR-Cas12a是一种RNA引导的基因组编辑工具.
- 它通过其RuvC核酶域创建双链DNA断裂.
- 目标DNA链穿越到RuvC核心的机制尚不清楚.
研究的目的:
- 阐明CRISPR-Cas12a中DNA目标链穿越的机制.
- 确定酶域在促进DNA分裂中的作用.
主要方法:
- 连续分子动力学模拟 (几十微秒).
- 自由能量模拟. 自由能量模拟.
- 在体外DNA裂变实验中.
主要成果:
- 在RuvC域内的一个alpha螺旋盖定并指导crRNA:DNA复合体.
- 该REC2域将双重驱动到酶核心.
- 努克域促进了RuvC核心内的目标链曲和适应.
结论:
- 阿尔法螺旋盖对于DNA目标链穿越至关重要.
- 这种机制解释了Cas12a如何实现精确的DNA裂变.
- 这些发现提高了基本的理解,并有助于基因组编辑工程.
相关概念视频
CRISPR
51.0K
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
51.0K
Homologous Recombination
50.5K
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...
50.5K
CRISPR and crRNAs
17.0K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
17.0K
DNA Helicases
21.3K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.3K


