Weak Fragment Crystallizable (Fc) Domain Interactions Drive the Dynamic Assembly of IgG Oligomers upon Antigen Recognition.,ACS Nano

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Weak Fragment Crystallizable (Fc) Domain Interactions Drive the Dynamic Assembly of IgG Oligomers upon Antigen Recognition.
ACS Nano ( IF 15.8 ) Pub Date : 2020-01-08 , DOI: 10.1021/acsnano.9b08347
Jürgen Strasser ₁ , Rob N de Jong ₂ , Frank J Beurskens ₂ , Janine Schuurman ₂ , Paul W H I Parren _{3,

4} , Peter Hinterdorfer ₅ , Johannes Preiner ₁

Affiliation

Activation of membrane receptors through clustering is a common mechanism found in various biological systems. Spatial proximity of receptors may be transduced across the membrane to initiate signaling pathways or alternatively be recognized by peripheral proteins or immune cells to trigger external effector functions. Here we show how specific immunoglobulin G (IgG) binding induces clustering of monomeric target molecules in lipid membranes through Fc-Fc interactions. We visualize and characterize the dynamic IgG oligomerization process and the molecular interactions involved using high-speed atomic force microscopy, single-molecule force spectroscopy, and quartz crystal microbalance experiments. We found that the Fc-Fc interaction strength is precisely tuned to be weak enough to prevent IgG oligomerization in solution at physiological titers, but enabling IgG oligomerization when Fabs additionally bind to their cognate surface epitopes, a mechanism that ultimately targets IgG-mediated effector functions such as classical complement activation to antigenic membranes.

中文翻译：

抗原识别后，弱片段可结晶（Fc）结构域相互作用驱动IgG低聚物的动态组装。

通过聚簇激活膜受体是在各种生物系统中发现的常见机制。受体的空间邻近性可以跨膜转导以启动信号传导途径，或者被周围的蛋白质或免疫细胞识别以触发外部效应子功能。在这里，我们显示特异性免疫球蛋白G（IgG）结合如何通过Fc-Fc相互作用诱导脂质膜中的单体靶分子聚集。我们使用高速原子力显微镜，单分子力光谱和石英晶体微量天平实验来可视化和表征动态IgG低聚过程以及涉及的分子相互作用。我们发现Fc-Fc相互作用强度经过精确调整，足以防止生理滴度下溶液中IgG寡聚，

更新日期：2019-12-30

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