合作折叠作为进化抗体结合剂中的分子开关
Malin Jönsson1, Ameeq Ul Mushtaq2, Tamás Milán Nagy2
1Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden.
The Journal of biological chemistry
|September 21, 2024
概括
研究人员设计了一种新型抗体结合蛋白,具有激活的"开启/关闭"开关. 这一蛋白质工程的突破使得能控制的可调节蛋白质活性成为可能,从而推动了生物技术的应用.
科学领域:
- 生物技术是生物技术.
- 蛋白质工程是指蛋白质工程.
- 分子生物学分子生物学
背景情况:
- 设计由外部线索控制的可调节活动的蛋白质是一个重要的生物技术挑战.
- 像calmodulin这样的自然存在的蛋白质对表现出全反应,作为分子开关的灵感.
研究的目的:
- 用一种依赖的分子开关来设计一个小的抗体结合域.
- 为了创建由存在或不存在控制的有条件抗体亲和力的蛋白质变体.
主要方法:
- 半理性蛋白质设计与定向进化相结合.
- 设计了一个结合循环进入蛋白质G域.
- 利用设计的选择策略,对条件抗体结合产生负和正选择压力.
主要成果:
- 开发出具有依赖抗体亲和力的新型蛋白质变体,作为分子"开/关"开关.
- 核磁共振光谱学揭示了一种结合和折叠机制,控制了目标结合表面的功能.
- 观察了合作折叠机制的演变,以应对选择压力.
结论:
- 具有条件目标相互作用的工程可切换蛋白质为生物技术应用提供了精致的可调节控制.
- 了解调节相互作用的分子机制是开发先进可切换蛋白质的关键.
- 合作折叠机制是自然进化的有效解决方案,用于微调的宏分子识别.
更多相关视频
10:17Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library
Published on: January 14, 2020
7.7K
12:28Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments
Published on: October 15, 2016
11.5K
相关概念视频
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
Protein Folding
117.7K
Overview
117.7K
Noncovalent Attractions in Biomolecules
49.5K
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,...
49.5K
Antibody Structure
59.6K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
59.6K
Molecular Chaperones and Protein Folding
17.8K
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...
17.8K
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
