Cryo-EM structures of two human B cell receptor isotypes
Cryo-EM structures of two human B cell receptor isotypes
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DOI：
10.1126/science.abo3828
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发表时间：
2022-08-19
期刊：
影响因子：
56.9
通讯作者：
Huang, Zhiwei
中科院分区：
文献类型：
--
作者：
Ma, Xinyu;Zhu, Yuwei;Huang, Zhiwei
B细胞受体（BCR）复合物在B细胞发育和免疫应答中起关键作用。BCR复合物的组装机制尚不清楚。我们以1:1的化学计量测定了人IgG-BCR和IgM-BCR的低温电镜（cro - em）结构，它们由膜结合免疫球蛋白分子（mIg）和Ig α / β亚基组成。这两种BCR复合物的组装涉及它们的细胞外结构域、膜-近端连接肽和跨膜螺旋。mIgG和mIgM的TM螺旋与Ig α / β TM螺旋共享一组保守的疏水和极性相互作用。相比之下，IgG-C γ 3和IgM-Cm4结构域分别通过头尾和并排模式与细胞外的Ig α / β样结构域相互作用。这项工作揭示了BCR组装的结构基础，并为BCR触发提供了见解。
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 Ig alpha/beta 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 Ig alpha/beta TM helices. By contrast, the IgG-C gamma 3 and IgM-Cm4 domains interact with extracellular Ig-like domains of Ig alpha/beta 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.