研究人员报告了静息状态下人类免疫球蛋白M-B细胞受体（IgM-BCR）的3.3埃冷冻电镜结构。IgM-BCR包括两条重链、两条轻链和Igα/Igβ异构体。重链的外域与Igα/Igβ的外域紧密堆叠，一条重链锁在Igα和Igβ的并膜区之间。细胞外的相互作用可能决定了BCR的同型特异性。IgM-BCR的跨膜螺旋形成一个四螺旋束，似乎在所有BCR同型中都是保守的。这个结构包含了IgM-BCR外延上的14个糖基化位点，并揭示了三个潜在的表面结合位点。
这项工作揭示了BCR的组织原理，并可能促进基于抗体的治疗方法设计。
据介绍，BCR通过识别抗原启动免疫反应。
附：英文原文
Title: Cryo-EM structure of the human IgM B cell receptor
Author: Qiang Su, Mengying Chen, Yan Shi, Xiaofeng Zhang, Gaoxingyu Huang, Bangdong Huang, Dongwei Liu, Zhangsuo Liu, Yigong Shi
Issue&Volume: 2022-08-19
Abstract: The B cell receptor (BCR) initiates immune responses through antigen recognition. We report a 3.3-angstrom cryo–electron microscopy structure of human immunoglobulin M (IgM)–BCR in the resting state. IgM-BCR comprises two heavy chains, two light chains, and the Igα/Igβ heterodimer. The ectodomains of the heavy chains closely stack against those of Igα/Igβ, with one heavy chain locked between Igα and Igβ in the juxtamembrane region. Extracellular interactions may determine isotype specificity of the BCR. The transmembrane helices of IgM-BCR form a four-helix bundle that appears to be conserved among all BCR isotypes. This structure contains 14 glycosylation sites on the IgM-BCR ectodomains and reveals three potential surface binding sites. Our work reveals the organizational principles of the BCR and may facilitate the design of antibody-based therapeutics.
DOI: abo3923
Source: https://www.science.org/doi/10.1126/science.abo3923