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

doi:10.1126/science.abd9836

GSTDTAP > 气候变化

DOI	10.1126/science.abd9836
	Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81
	Katherine J. Susa; Shaun Rawson; Andrew C. Kruse; Stephen C. Blacklow
	2021-01-15
发表期刊	Science
出版年	2021
英文摘要	A core component of the immune system are B cells, which are activated by infection and then mature to provide long-lived immunity. Activation is initiated when a cell surface B cell receptor, in association with its coreceptor, recognizes an antigen. Susa et al. report a structure of the B cell receptor CD81 in complex with its co receptor, CD19. CD81 alone binds to cholesterol, but the conformational changes associated with binding to CD19 occlude the cholesterol-binding pocket. Regulating cholesterol binding could play a role in the activation mechanism. The structure also provides a basis for the design of immunotherapies. Science , this issue p. [300][1] 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. [1]: /lookup/doi/10.1126/science.abd9836
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/311510
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Katherine J. Susa,Shaun Rawson,Andrew C. Kruse,et al. Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81[J]. Science,2021.
APA	Katherine J. Susa,Shaun Rawson,Andrew C. Kruse,&Stephen C. Blacklow.(2021).Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81.Science.
MLA	Katherine J. Susa,et al."Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81".Science (2021).