确定细胞活动的RNA构造性倾向
Megan L Ken1, Rohit Roy2, Ainan Geng1
1Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA.
Nature
|May 17, 2023
概括
细胞活动依赖于生物分子相互作用,而生物分子相互作用受到结构变化的影响. 这项研究量化了HIV-1 TAR RNA中的这些变化,将它们与结合 afinity 和病毒转活联系起来.
科学领域:
- 分子生物学
- 生物物理
- 结构生物学
背景情况:
- 细胞过程依赖于生物分子相互作用形成活性复合体.
- 分子间接触调解这些相互作用, 而它们的干扰改变了细胞生理.
- 生物分子相互作用往往需要构造变化,影响结合亲和力和细胞活动.
研究的目的:
- 系统地改变和量化HIV-1 TAR RNA的结构性倾向.
- 确定基于组合的构造性倾向在细胞活动中的作用.
- 调查构造状态如何影响结合亲和力和HIV-1 Tat依赖的交换活化.
主要方法:
- 艾滋病毒-1 TAR RNA 形状的系统性改变.
- 对形状倾向的定量测量.
- 评估与HIV-1 Tat蛋白的RNA结合区域的结合关系.
- 在细胞模型中测量HIV-1 Tat依赖的交换活化.
主要成果:
- 系统地改变并确定了HIV- 1 TAR RNA的构造性倾向.
- 这些倾向准确地预测了TAR RNA与Tat蛋白之间的结合亲和关系.
- 这项研究成功预测了HIV- 1 Tat依赖性转活的程度.
- 一种异常罕见且短暂的RNA构造状态被确定为驱动细胞过程.
结论:
- 基于组合的形状倾向在细胞活动中起着关键作用.
- 了解形态动力学对于建模生物结合能量学至关重要.
- 这项工作为评估构造状态对生物功能的影响提供了定量框架.
- 这些发现突显了生物过程中罕见的构造状态的重要性.
相关概念视频
01:29The Two-State Receptor Model
2.0K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
2.0K
01:22Protein Folding
118.6K
Overview
118.6K
01:49Conserved Binding Sites
4.3K
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...
4.3K
01:58Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
02:13Cooperative Binding of Transcription Regulators
6.5K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.5K