RNA G-四重复折叠是一个多路径过程,由构造驱动.
Marijana Ugrina1,2, Ines Burkhart3, Diana Müller3
1Institute of Physics, University of Augsburg, Universitätsstraße 1, 86159 Augsburg, Germany.
Nucleic acids research
|November 21, 2023
概括
通过模拟和实验阐明了RNA G-四重复 (rG4) 折叠路径. 合规驱动了分支折叠,揭示了rG4函数的关键中间体.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 调节性RNA的功能,如RNA G-四重复合体 (rG4s),取决于它们的折叠动态.
- 了解rG4折叠路径对于破译它们的生物作用至关重要.
研究的目的:
- 来自端粒重复含RNA (TERRA25) 的G-四重复的折叠路径的特征.
- 开发和验证一种方法,以精确模拟在离子大气层的存在下rG4折叠.
主要方法:
- 结合了全原子分子动力学和粗粒度模拟与循环二元化实验.
- 开发了基于水的所有原子模拟的隐性溶剂粗粒模拟的匹配程序,以捕获离子双层.
- 利用每核酸3个位点的粗粒度模拟来解决折叠路径和中间状态.
主要成果:
- 在模拟和实验数据之间实现了对不同盐度和温度的折叠/展开状态种群的定量一致.
- 识别了中间状态,包括由短暂的Hoogsteen相互作用稳定的针头,三重和双针头结构.
- 揭示了折叠通过每个通路的两个通路中间体进行.
结论:
- 形态是分支,多路径折叠过程的关键驱动因素,在像TERRA25这样的rG4中观察到.
- 开发的模拟方法精确地捕捉了rG4折叠动力学和中间状态.
- 该研究提供了对具有不同循环长度的多个rG4系统的折叠动态的见解.
相关概念视频
Protein Folding
8.1K
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...
8.1K
Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
Molecular Chaperones and Protein Folding
18.0K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.0K
RNA Structure
4.8K
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
4.8K
Proteins: From Genes to Degradation
12.3K
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
Transcription is the synthesis of RNA...
12.3K
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K


