研究人员确定了人类IgG- B细胞受体（BCR）和IgM-BCR的冷冻电镜（cryo-EM）结构，它们由膜结合的免疫球蛋白分子（mIg）和Igα/β亚单位以1：1的比例组成。这两种BCR复合物的组装涉及到它们的细胞外结构域、膜近端连接肽和跨膜（TM）螺旋。mIgG和mIgM的TM螺旋与Igα/β的TM螺旋共享一套保守的疏水和极性相互作用。相比之下，IgG-Cγ3和IgM-Cμ4结构域分别通过头对尾和并排模式与Igα/β的胞外Ig样结构域相互作用。
这项工作揭示了BCR组装的结构基础，并提供了对BCR触发的深入了解。
据了解，BCR复合物在B细胞发育和免疫反应中起着关键作用。BCR复合物的组装机制仍然未知。
附：英文原文
Title: Cryo-EM structures of two human B cell receptor isotypes
Author: Xinyu Ma, Yuwei Zhu, De Dong, Yan Chen, Shubo Wang, Dehui Yang, Zhuo Ma, Anqi Zhang, Fan Zhang, Changyou Guo, Zhiwei Huang
Issue&Volume: 2022-08-19
Abstract: The B cell receptor (BCR) complex plays a critical role in B cell development and immune responses. The assembly mechanisms underlying the BCR complex remain unknown. We determined the cryo–electron microscopy (cryo-EM) structures of human IgG-BCR and IgM-BCR, which consist of membrane-bound immunoglobulin molecules (mIg) and Igα/β subunits at a 1:1 stoichiometry. Assembly of both BCR complexes involves their extracellular domains, membrane-proximal connection peptides, and transmembrane (TM) helices. The TM helices of mIgG and mIgM share a conserved set of hydrophobic and polar interactions with Igα/β TM helices. By contrast, the IgG-Cγ3 and IgM-Cμ4 domains interact with extracellular Ig-like domains of Igα/β through head-to-tail and side-by-side modes, respectively. This work reveals the structural basis for BCR assembly and provides insights into BCR triggering.
DOI: abo3828
Source: https://www.science.org/doi/10.1126/science.abo3828