工具抗体碎片揭示了罗多普辛-Gi信号复合体的多种构造
Filip Pamula1, Oliver Tejero1, Jonas Mühle2
1Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland; Department of Biology, ETH Zürich, Zürich, Switzerland.
Biophysical journal
|October 1, 2025
概括
两种新的抗体片段Fab79和Fab13被开发用于研究G蛋白合受体 (GPCR) 信号复合体. 这些碎片稳定或调节这些复合体,为G蛋白激活和动态提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子药理学分子药理学
背景情况:
- 抗体碎片 (Fabs) 是研究蛋白质相互作用的关键工具,特别是G-蛋白结合受体 (GPCR) 信号复合体.
- 使用Fabs针对这些复合体的不同组件可以揭示构造调节和动态.
研究的目的:
- 在生物化学和结构上描述两个新的Fab片段,Fab79和Fab13,针对罗多素-Gαiβγ复合体.
- 研究这些Fabs在稳定或调节GPCR信号复合体和探测G蛋白激活状态方面的潜力.
主要方法:
- 生物化学测试以评估结合和复合稳定性.
- 电子显微镜 (cryo-EM) 用于确定Fab结合复合体的高分辨率结构.
- 与Gαiβγ复合体的特定子单元的Fab相互作用的表征.
主要成果:
- Fab79结合了Gαi的α-螺旋域 (AHD),阻碍了其闭合并防止了复杂解离,从而稳定了激活状态.
- Fab13在没有与Gα或受体直接相互作用的情况下,刚性地与Gβ亚单元结合.
- 这两种Fab都有效地揭示了G蛋白激活的功能相关的构造状态.
结论:
- Fab79和Fab13是稳定和调节GPCR信号复合体的宝贵工具.
- 这些Fabs为了解G蛋白激活的结构动态提供了新的途径.
- 这些结合物的表征推动了GPCRs的结构和功能研究.
相关概念视频
01:11Channel Rhodopsins
3.1K
Most organisms use photoreceptors to sense and respond to light. Examples of photoreceptors include bacteriorhodopsins and bacteriophytochromes in some bacteria, phytochromes in plants, and rhodopsins in the photoreceptor cells of the vertebral retina. The light-sensitive property of these receptors is because of the bound chromophores, such as bilin in the phytochromes and retinal in the rhodopsins.
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
3.1K
01:30Assembly of Signaling Complexes
6.5K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.5K
01:10Antibody Structure
65.3K
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...
65.3K