FcεRI绑定IgE的冷EM结构揭示了Fab-Fc杆的多个定义的构造
Rasmus K Jensen1,2, Michaela Miehe3, Rosaria Gandini1
1Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Allergy
|November 7, 2025
概括
这项研究揭示了IgE抗体与其FcεRIα受体结合的完整结构,揭示了抗体的Fab臂中的新动态. 这些发现为开发先进的抗IgE过敏疗法提供了洞察力.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 免疫球蛋白E (IgE) 是过敏反应的核心.
- 之前的研究详细介绍了IgE Fc片段和FcεRIαectodomain相互作用.
- 结合FcεRIα的完整IgE抗体的行为仍然没有表征.
研究的目的:
- 阐明与其受体FcεRIα复合的全尺寸IgE抗体的结构结构.
- 研究IgE在受体结合时的动态特性和构造格局.
主要方法:
- 结合晶体学,冷电子显微镜 (cryo-EM) 和负染色EM (ns-EM) 进行结构分析.
- 使用介质释放和CD23结合试验来评估IgE变体活性.
主要成果:
- 获得了全IgE FcεRIα复合体的10个冷EM结构,揭示了T型形状.
- 在ns-EM中观察到显著的Fab臂旋转 (高达40°) 和明显的Fab臂排列.
- 证明增加Fab-Fc链灵活性不会影响IgE生物活性.
结论:
- 描述了全IgE-FcεRIα复合体的架构,引入了FcεRIα结合IgE的新动态.
- 与完整的受体结构相比,突出了FcεRIαectodomain方向的构造差异.
- 这些发现为开发针对过敏性疾病的新型抗IgE疗法提供了基础.
相关概念视频
Cryo-electron Microscopy
4.1K
Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
4.1K
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
Immunoglobulin-like Cell Adhesion Molecules
4.1K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
4.1K
Antibody Structure and Classes
8.1K
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
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.
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.
8.1K
Structure of Cadherins
4.6K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
4.6K
Fischer Projections
16.1K
Learning to draw Fischer projections of molecules and understanding their relevance plays a crucial role in the visual depiction of organic molecules. A Fischer projection is a two-dimensional projection on a planar surface to simplify the three-dimensional wedge–dash representation of molecules. This is especially helpful in the case of molecules with multiple chiral centers that can be difficult to draw. Here, all the bonds of interest are represented as horizontal or vertical lines. While...
16.1K


