期刊
SCIENCE
卷 371, 期 6526, 页码 300-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd9836
关键词
-
资金
- NIH [R35 CA220340, F31 HL147459, DP5 OD021345]
The structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment was determined by cryo-electron microscopy, revealing the contact interface between the ectodomains and the conformational changes of CD81 upon binding to CD19. This provides insights into the assembly of the CD19-CD81 complex and offers a basis for designing therapies for B cell dysfunction.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据