血细胞衍生HBsAg特异性抗体的表征及其与本源HBsAg二分体结合的结构基础
Bin Ju1,2, Zhouqing Liu3, Hu Yan4
1Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China zhangzheng1975@aliyun.com jubin2013@163.com liaomf@sustech.edu.cn yuchenxia@whu.edu.cn.
研究人员确定了血细胞衍生的单克隆抗体 (mAbs),向乙型肝炎表面抗原 (HBsAg). 这些mAbs对HBV基因型表现出广泛的活性,并提供了对HBsAg结合的结构洞察力,提供了潜在的新抗体疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 针对乙型肝炎表面抗原 (HBsAg) 的等离子体衍生单克隆抗体 (mAbs) 和它们与原生HBsAg的结合机制尚不清楚.
- 抗体与HBsAg结合的结构基础对于开发有效的乙型肝炎病毒 (HBV) 疗法至关重要.
研究的目的:
- 为了识别来自等离子体的HBsAg特异性mAbs.
- 评估这些mAbs.的抗病毒活性.
- 为了确定这些与本地HBsAg结合的mAbs的结构.
主要方法:
- 从接种疫苗的个体的血细胞中克隆和表达mAbs.
- 分析mAb基因特征,交叉基因型结合和抗病毒功能 (体外和体内).
- 低温电子显微镜 (cryo-EM) 用于解析mAb-HBsAg复合物的结构.
主要成果:
- 一系列HBsAg特异的mAbs从血细胞中克隆,表现出对各种HBV基因型的交叉反应性.
- 这些mAbs表现出抗病毒功能,包括中和和抗体依赖的细胞化.
- 化EM揭示了代表性mAb (SY-23) 与二度HBsAg的结合机制,包括主要抗原循环 (AGL) 的前所未有的细节.
结论:
- 该研究确定了来自等离子体的mAbs的多种基因特征和抗HBV活性,呈现出潜在的抗体药物候选者.
- 确定HBsAg AGL的原子模型为了解HBV感染和免疫反应期间其构造动态提供了基础.
- 这些发现推动了针对乙型肝炎的基于抗体的新型治疗方法的开发.
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
09:07Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
相关概念视频
Antibody Structure
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...
Cooperative Binding of Transcription Regulators
Antibody Structure and Classes
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
Inheritance of Chromatin Structures
Structures of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
The Equilibrium Binding Constant and Binding Strength
