展开合作和结合的决定因素被解在DNA结合域中
Divya Rajendran1, Saloni Goyal1, Dhruv Kumar Chaurasiya1
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
The journal of physical chemistry. B
|September 23, 2024
概括
在果糖抑制剂 (FruR) 蛋白DBD中堆叠的Tyr-Tyr稳定了部分折叠的状态. 破坏这种相互作用会导致蛋白质的失序,但DNA结合仍然相似,突出显示了DNA的陪伴者作用.
科学领域:
- 蛋白质的结构和动态.
- 生物物理学的生物物理.
- 分子生物学分子生物学
背景情况:
- 蛋白质折叠是由非共价相互作用控制的.
- 果糖抑制剂 (FruR) 的DNA结合域 (DBD) 具有独特的三余插入 (KQY).
- 这种插入创建了一个Tyr-Tyr堆叠相互作用,在相关蛋白质中不存在.
研究的目的:
- 调查Tyr-Tyr堆叠在FruR DBD稳定性和功能中的作用.
- 描述破坏这种相互作用对蛋白质结构和DNA结合的影响.
- 探索DNA对改变蛋白质状态的影响.
主要方法:
- 将实验技术与分子模拟相结合.
- 使用生物物理探针来评估蛋白质的稳定性和展开.
- 采用氨酸突变生成来破坏Tyr-Tyr堆叠相互作用.
- 在结合状态中分析DNA结合亲和力和二次结构变化.
主要成果:
- 泰尔-泰尔堆叠局部化稳定能量,导致脱的展开和稳定的中间体.
- 破坏Tyr-Tyr堆叠会产生一个融化的球状状态,具有非本地相互作用和高波动.
- 化的球状变体与野生类型的FruR DBD相似的亲和力结合了DNA.
- 结合DNA会诱导变体中的二次结构发生变化,这表明伴侣效应.
结论:
- 泰尔-泰尔堆叠相互作用对FruR DBD稳定性,合作性和微调结合至关重要.
- 尽管看起来几乎是无序的,但FruR DBD是通过这种芳香相互作用来稳定.
- DNA的静电电位作为伴侣,促进了不稳定的蛋白质变体的结合.
相关概念视频
Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K
Cooperative 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
Single-Strand DNA Binding Proteins
14.0K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.0K
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
Noncovalent Attractions in Biomolecules
49.4K
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,...
49.4K
DNA Topoisomerases
31.1K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.1K


