相关实验视频
Updated: Jan 11, 2026
05:49
Protein Engineering by Yeast Surface Display
Published on: November 29, 2024
3.3K
兰巴 (λ) 抗体轻链的单残留工程减少了形状灵活性,提高了热稳定性
Yead Jewel1, Tynan Young1, Miso Park1
1Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States.
Computational and structural biotechnology journal
|November 17, 2025
概括
工程兰巴达轻链抗体显示出更好的稳定性. 一个单一的甘氨酸突变增强了热稳定性,而不影响抗原结合,有助于治疗的发展.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 带有兰巴达 (λ) 轻链的单克隆抗体由于其生物物理稳定性低于卡帕 (κ) 变体,因此在治疗上使用率较低.
- 法布片段的形状灵活性,特别是肘部角度,有助于减少 λ 轻链的稳定性.
研究的目的:
- 为了确定影响 λ 轻链中的 Fab 肘角转换的关键残留物.
- 开发一种提高基于 λ 的治疗抗体生物物理稳定性的策略.
主要方法:
- 微秒级分子动力学模拟EBV中和Fab AMMO1.1.
- 位点定向的突变发生 (Gly111 到 氨酸).
- 晶体学,微分扫描度学和表面等离子体共振用于结构和生物物理特征.
主要成果:
- 在 λ 轻链链中的位置111 (Gly111) 中保存的甘氨酸被确定为大规模的 Fab 肘角转换的关键.
- G111T突变增加了自由能量屏障,减少了形状转换,并提高了高达2.5°C的热稳定性.
- 这种突变在第二个 λ-Fab 中得到验证,并通过模拟显示,在临床 λ-Fabs 中降低了灵活性,而不会影响抗原结合.
结论:
- 一个可通用的单一残留工程策略可以提高基于λ的Fabs的稳定性.
- 这种方法提高了热稳定性,减少了形状灵活性,而不会牺牲抗体功能.
- 这些发现对基于λ的治疗抗体的开发和制造能力有重大影响.
更多相关视频
12:28Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments
Published on: October 15, 2016
12.0K
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
8.2K
相关概念视频
01:10Antibody Structure
65.2K
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...
65.2K
01:49Conserved Binding Sites
5.0K
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...
5.0K
01:25Protein Folding
11.0K
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...
11.0K