美国哈佛医学院Stephen C. Blacklow和Andrew C. Kruse研究组合作在研究中取得进展。他们解析了与四跨膜蛋白CD81结合的B细胞共受体CD19的冷冻电镜（cryo-EM）结构。该项研究成果发表在2021年1月15日出版的《科学》杂志上。

他们报道了一个3.8埃CD19-CD81复合物与治疗性抗原结合片段的结合的cryo-EM结构。 该结构既包括复合物的细胞外结构域，又包括跨膜螺旋，揭示了驱动复合物形成的胞外域之间的接触界面。与CD19结合后，CD81打开其胞外域以暴露疏水性CD19结合表面，并重新组织其跨膜螺旋，以封闭载脂蛋白中存在的胆固醇结合口袋。

他们的数据揭示了CD19-CD81复合物装配的结构基础，为合理设计B细胞功能障碍的疗法提供了基础。

研究人员表示，通过CD19-CD81共受体复合物与B细胞受体的信号传递，是B细胞发育和激活的关键决定因素。尚不知道CD81如何与CD19结合以实现共受体功能。

附：英文原文

Title: Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81

Author: Katherine J. Susa, Shaun Rawson, Andrew C. Kruse, Stephen C. Blacklow

Issue&Volume: 2021/01/15

Abstract: Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to enable co-receptor function. Here, we report a 3.8-angstrom structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment, determined by cryo–electron microscopy (cryo-EM). The structure includes both the extracellular domains and the transmembrane helices of the complex, revealing a contact interface between the ectodomains that drives complex formation. Upon binding to CD19, CD81 opens its ectodomain to expose a hydrophobic CD19-binding surface and reorganizes its transmembrane helices to occlude a cholesterol binding pocket present in the apoprotein. Our data reveal the structural basis for CD19-CD81 complex assembly, providing a foundation for rational design of therapies for B cell dysfunction.

DOI: 10.1126/science.abd9836

Source: https://science.sciencemag.org/content/371/6526/300