结构机制和关于多个纳米体结合多种SOD1表位的结构机制和见解
Shihao Cheng1, Chao Zhong1, Haoran Zhu1
1State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai, China.
Communications biology
|December 5, 2025
概括
研究人员开发了纳米体,以向铜/超氧化物脱酶 (SOD1),这是与肌缩性侧面硬化症 (ALS) 相关的蛋白质. 这些纳米体以高亲和力结合SOD1,为ALS诊断和治疗提供了潜在的工具.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- 铜/超氧化物脱酶 (SOD1) 对于减轻氧化应激至关重要.
- SOD1突变和聚合与肌缩性侧面硬化症 (ALS) 病原发生有关.
- 纳米体为致病性SOD1.1提供了有针对性的治疗策略.
研究的目的:
- 为了确定SOD1与纳米体复合的高分辨率晶体结构.
- 描述单个和多元纳米体与SOD1.1的结合亲和力和相互作用.
- 建立一个开发基于纳米体的ALS工具的基础.
主要方法:
- 用X射线晶体学来确定复杂的结构.
- 异热定位热量测量 (ITC) 和光检测尺寸排除色谱 (FSEC) 用于结合亲和力.
- 动态光散射 (DLS) 用于复杂的稳定性.
主要成果:
- SOD1-纳米体复合体的第一个高分辨率的晶体结构 (1:2和1:3固态度).
- 纳米体与SOD1结合,具有纳米分子亲和力 (KD 23.2 nM至529 nM).
- 工程双重纳米体实现了更高的亲和力 (KD 4.39 nM) 没有固态干扰.
结论:
- 对SOD1.1的多纳米体准的原子分辨率洞察力.
- 证明了SOD1-纳米体复合物的高亲和结合和合稳定性.
- 为开发针对ALS和神经退行性疾病的SOD1向工具提供了基础.
更多相关视频
11:05Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
Published on: February 21, 2019
9.6K
08:09Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
9.9K
相关概念视频
Ligand Binding and Linkage
5.4K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.4K
Antibody Actions
2.3K
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
2.3K
Conserved 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
Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
Cross-reactivity
32.8K
Overview
32.8K
Antibody 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
