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-Structure paper
| タイトル | Orientation-dependent CD45 inhibition with viral and engineered ligands. |
|---|---|
| ジャーナル・号・ページ | Sci Immunol, Vol. 9, Issue 100, Page eadp0707, Year 2024 |
| 掲載日 | 2024年10月25日 |
著者 | Marta T Borowska / Liu D Liu / Nathanael A Caveney / Kevin M Jude / Won-Ju Kim / Takeya Masubuchi / Enfu Hui / Robbie G Majzner / K Christopher Garcia / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Sci Immunol / PubMed:39454026 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.8 Å |
| 構造データ | EMDB-43497, PDB-8vse: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | IMMUNE SYSTEM / Complex / T cell signaling / Viral suppression |
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homo sapiens (ヒト)
human adenovirus 19a (ヒトアデノウイルス)
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