人体IgM B细胞受体的冷EM结构

Qiang Su1,2, Mengying Chen3, Yan Shi1,2,4

  • 1Research Center for Industries of the Future, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Xihu District, Hangzhou 310024, Zhejiang Province, China.

Science (New York, N.Y.)
|August 18, 2022
PubMed

Insights

研究人员揭示了B细胞受体 (BCR) 的休息结构,特别是免疫球蛋白M (IgM) -BCR. 这种对BCR组织的结构洞察力可能有助于开发基于抗体的新疗法.

科学领域:

  • 免疫学
  • 结构生物学
  • 生物化学

背景情况:

  • B细胞受体 (BCR) 对于通过抗原识别启动适应性免疫反应至关重要.
  • 了解BCR结构是解读免疫信号通路的关键.

研究的目的:

  • 确定人类免疫球蛋白M (IgM) -BCR在静止状态中的高分辨率冷电子显微镜结构.
  • 阐明管理BCR组装和功能的组织原则.

主要方法:

  • 使用冷电子显微镜 (cryo-EM) 来获得人类静止IgM-BCR的3. 3安格斯特罗姆结构.
  • 详细的结构分析侧重于重链,轻链和Igα/Igβ信号组件之间的相互作用.

主要成果:

  • 该结构显示IgM-BCR由两个重链,两个轻链和Igα/Igβ异构体组成.
  • 在重链ectodomains和Igα/Igβ异构体之间发现了特定的相互作用,其中包括在柔膜区域的独特相互作用.
  • 在跨BCR同型的跨膜域中观察到一个保存的四螺旋束结构.
  • 该结构突出显示了14个糖化位点和3个潜在的IgM-BCR外接位点.

结论:

  • 确定结构为IgM-BCR的静止状态组织提供了前所未有的洞察力.
  • 这些发现揭示了BCR功能的分子基础,并可能指导基于抗体的新疗法的开发.
抽象的

No abstract available in PubMed .

相关概念视频

Antibody Structure01:10

Antibody Structure

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...
61.1K
Antibody Structure and Classes01:25

Antibody Structure and Classes

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.
3.6K
Cryo-electron Microscopy01:28

Cryo-electron Microscopy

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...
3.5K
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
754
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

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...
3.4K
Transcytosis of IgG01:15

Transcytosis of IgG

Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
2.9K