特定的蛋白质-RNA相互作用大多保留在生物分子凝聚物中
Tebbe de Vries1, Mihajlo Novakovic1, Yinan Ni1
1Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
Science advances
|March 6, 2024
概括
我们开发了一种新的方法,LLPS-CLIR-MS,研究RNA结合蛋白 (RBPs) 和RNA如何在生物分子凝聚物中相互作用. 这种技术揭示了这些相互作用在相位分离过程中如何变化.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 生物分子凝聚物是关键的细胞区,通常依赖于RNA和RNA结合蛋白 (RBPs).
- 了解驱动相分离的分子间相互作用及其对RBP和RNA的影响是有限的.
- 在这些动态结构中描述蛋白质-RNA相互作用仍然是一个挑战.
研究的目的:
- 开发和验证一种用于表征生物分子凝聚物的蛋白质-RNA相互作用的新方法.
- 为了研究在液-液相分离 (LLPS) 过程中RNA结合蛋白-RNA复合体凝结的结构后果.
主要方法:
- 开发了LLPS-CLIR-MS (同位素标记RNA的交联和相隔系统的双重质谱学).
- 应用LLPS-CLIR-MS以分析残留物特定分辨率在生物分子凝聚物内的分子间相互作用.
- 比较了凝聚相与分散相中的蛋白质-RNA相互作用.
主要成果:
- LLPS-CLIR-MS成功地描述了生物分子凝结体内的分子间相互作用.
- 序列特定的RNA结合蛋白-RNA相互作用通常保留在凝结物中.
- 确定了蛋白质-RNA接口的结构变化,包括凝结阶段的新型非特异性接触.
结论:
- LLPS-CLIR-MS提供了对生物分子凝聚物的蛋白质-RNA相互作用的残留特异性见解.
- 凝结改变了蛋白质-RNA接口,引入了新的相互作用.
- 这种方法对于结合性结构建模在缩形式的核糖核蛋白 (RNP) 是至关重要的.
相关概念视频
Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
RNA Stability
33.5K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.5K
Noncovalent Attractions in Biomolecules
50.6K
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
50.6K
Protein Folding
8.0K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.0K
Conservation of Protein Domains Over Different Proteins
10.9K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.9K
Ribosomal RNA Synthesis
13.2K
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
13.2K


