北京大学肖俊宇等合作近期取得重要工作进展，他们对高亲和力IgE受体FcεRI复合物进行了结构解析。相关研究成果2024年8月21日在线发表于《自然》杂志上。

据介绍，免疫球蛋白E（IgE）在过敏反应中起着关键作用。肥大细胞和嗜碱性粒细胞上发现的高亲和力IgE受体FcεRI是IgE效应器功能的核心。FcεRI是一种四聚体复合物，由FcεRIα、FcεRIβ和FcRγ的同二聚体（最初称为FcεRIγ）组成，FcεRIα识别IgE的Fc区（Fcε），FcεR1β-FcRγ促进信号转导。此外，FcRγ是其他免疫球蛋白受体的重要组成部分，包括IgG（FcγRI和FcγRIIIA）和IgA（FcαRI）的受体。然而，FcεRI组装的分子基础和FcRγ的结构仍然不清楚。

研究人员阐明了Fcε-FcεRI复合物的冷冻电镜结构。FcεRIα在受体的组装中起着至关重要的作用，与FcεRIβ和两个FcRγ亚基相互作用。FcεRIβ的结构为紧凑的四螺旋束，类似于B细胞抗原CD20。FcRγ二聚体呈现不对称结构，与FcεRIα的跨膜区卷曲形成三螺旋束。胆固醇样分子增强FcεRIβ和FcεRIα-FcRγ复合物之间的相互作用。突变分析进一步表明，FcRγ与FcεRIα和FcγRIIIA的相互作用之间存在相似性，但与FcαRI的相互作用存在差异。

总之，这一研究加深了人们对FcεRI信号机制的理解，并为依赖FcRα的其他免疫受体的功能提供了见解。

附：英文原文

Title: Structural insights into the high-affinity IgE receptor FcεRI complex

Author: Deng, Meijie, Du, Shuo, Hou, Handi, Xiao, Junyu

Issue&Volume: 2024-08-21

Abstract: Immunoglobulin E (IgE) plays a pivotal role in allergic responses1,2. The high-affinity IgE receptor, FcεRI, found on mast cells and basophils, is central to the effector functions of IgE. FcεRI is a tetrameric complex, comprising FcεRIα, FcεRIβ and a homodimer of FcRγ (originally known as FcεRIγ), with FcεRIα recognizing the Fc region of IgE (Fcε) and FcεRIβ–FcRγ facilitating signal transduction3. Additionally, FcRγ is a crucial component of other immunoglobulin receptors, including those for IgG (FcγRI and FcγRIIIA) and IgA (FcαRI)4,5,6,7,8. However, the molecular basis of FcεRI assembly and the structure of FcRγ have remained elusive. Here we elucidate the cryogenic electron microscopy structure of the Fcε–FcεRI complex. FcεRIα has an essential role in the receptor’s assembly, interacting with FcεRIβ and both FcRγ subunits. FcεRIβ is structured as a compact four-helix bundle, similar to the Bcell antigen CD20. The FcRγ dimer exhibits an asymmetric architecture, and coils with the transmembrane region of FcεRIα to form a three-helix bundle. A cholesterol-like molecule enhances the interaction between FcεRIβ and the FcεRIα–FcRγ complex. Our mutagenesis analyses further indicate similarities between the interaction of FcRγ with FcεRIα and FcγRIIIA, but differences in that with FcαRI. These findings deepen our understanding of the signalling mechanisms of FcεRI and offer insights into the functionality of other immune receptors dependent on FcRγ.

DOI: 10.1038/s41586-024-07864-5

Source: https://www.nature.com/articles/s41586-024-07864-5