通过专门的AAA+ ATPase激活转化酶的分子基础
Álvaro de la Gándara1, Mercedes Spínola-Amilibia1, Lidia Araújo-Bazán1
1Centro de Investigaciones Biológicas Margarita Salas, CSIC, Madrid, Spain.
Nature
|June 26, 2024
概括
转移酶调节涉及AAA+ ATPase子单元控制DNA的整合. 这项研究揭示了IstB ATPase如何使用DNA变形和自我组装来激活IstA转换酶,从而实现精确的基因转移.
科学领域:
- 分子生物学
- 结构生物学
- 遗传学
背景情况:
- 转基因酶调解重要的遗传过程,如染色体重组和基因传播.
- 许多转移酶需要AAA+ ATPase子单元来调节功能,但机制尚不清楚.
研究的目的:
- 阐明 IstB AAA+ ATPase 调节 IS21 转化酶 (IstA) 的机制.
- 了解ATPase活动如何控制DNA结合,转酶招募和催化激活.
主要方法:
- 使用溶液和冷电子显微镜 (cryo-EM) 来确定转基因组复合物的结构.
- 研究了IstB ATPase的自我组合及其与目标DNA和IstA的相互作用.
主要成果:
- B ATPase 形成二聚体的五聚体,从而诱导目标DNA的显著曲率.
- IstB 分室的二元化形成了 S 形的 DNA 配置,将 IstA 招募到 ~ 1 MDa 转基因组中.
- 在 IstB-IstA 界面上触发了依赖于核酸的构造变化,激活了 DNA 链转移.
结论:
- 通过核酸控制的组合和DNA变形,AAA+ ATPase 调节器重塑DNA和转基因酶.
- 这种机制解释了调节器如何确保Tn7,Mu和CRISPR相关元素等多种转换系统的位点选择性和催化激活.
相关概念视频
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
DNA-only Transposons
14.4K
DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
The donor site from where the transposon is excised is either degraded or...
14.4K
Energy to Drive Translocation
2.1K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.1K
ATP Synthase: Structure
12.3K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
12.3K
ATP Synthase: Mechanism
14.4K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.4K
Overview of Transposition and Recombination
15.4K
Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
15.4K


