方向(向量空间)
化学
细胞生物学
生物
计算生物学
几何学
数学
作者
Marta T. Borowska,Liu Daisy Liu,Nathanael A. Caveney,Kevin M. Jude,Won‐Ju Kim,Takeya Masubuchi,Enfu Hui,Robbie G. Majzner,K. Christopher García
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-10-25
卷期号:9 (100)
标识
DOI:10.1126/sciimmunol.adp0707
摘要
CD45 is a cell surface phosphatase that shapes the T cell receptor signaling threshold but does not have a known ligand. A family of adenovirus proteins, including E3/49K, exploits CD45 to evade immunity by binding to the extracellular domain of CD45, resulting in the suppression of T cell signaling. We determined the cryo-EM structure of this complex and found that the E3/49K protein is composed of three immunoglobulin domains assembled as "beads on a string" that compel CD45 into a closely abutted dimer by cross-linking the CD45 D3 domain, leading to steric inhibition of its intracellular phosphatase activity. Inspired by the E3/49K mechanism, we engineered CD45 surrogate ligands that can fine-tune T cell activation by dimerizing CD45 into different orientations and proximities. The adenovirus E3/49K protein has taught us that, despite a lack of a known ligand, CD45 activity can be modulated by extracellular dimerizing ligands that perturb its phosphatase activity and alter T cell responses.
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