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DOI | 10.1126/science.aau2909 |
Structural basis of latent TGF-beta 1 presentation and activation by GARP on human regulatory T cells | |
Lienart, Stephanie1; Merceron, Romain2,3; Vanderaa, Christophe1; Lambert, Fanny1; Colau, Didier4; Stockis, Julie1,5; van der Woning, Bas6; De Haard, Hans6; Saunders, Michael6; Coulie, Pierre G.1,5; Savvides, Savvas N.2,3; Lucas, Sophie1,5 | |
2018-11-23 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6417页码:952-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Belgium |
英文摘要 | Transforming growth factor-beta 1 (TGF-beta 1) is one of very few cytokines produced in a latent form, requiring activation to exert any of its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (T-regs) suppress immune cells within close proximity by activating latent TGF-beta 1 presented by GARP (glycoprotein A repetitions predominant) to integrin alpha V beta 8 on their surface. We solved the crystal structure of GARP: latent TGF-beta 1 bound to an antibody that stabilizes the complex and blocks release of active TGF-beta 1. This finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-beta 1, to chaperone and orient the cytokine for binding and activation by alpha V beta 8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-beta 1 activation and immunosuppression by T-regs. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000451124500044 |
WOS关键词 | TGF-BETA ; PROTEINS ; SURFACE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200134 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.UCLouvain, de Duve Inst, B-1200 Brussels, Belgium; 2.Univ Ghent, Dept Biochem & Microbiol, B-9052 Ghent, Belgium; 3.VIB Ctr Inflammat Res, B-9052 Ghent, Belgium; 4.Ludwig Canc Res, Brussels, Belgium; 5.Walloon Excellence Lifesci & Biotechnol, B-1300 Wavre, Belgium; 6.Argenx, B-9052 Zwijnaarde, Belgium |
推荐引用方式 GB/T 7714 | Lienart, Stephanie,Merceron, Romain,Vanderaa, Christophe,et al. Structural basis of latent TGF-beta 1 presentation and activation by GARP on human regulatory T cells[J]. SCIENCE,2018,362(6417):952-+. |
APA | Lienart, Stephanie.,Merceron, Romain.,Vanderaa, Christophe.,Lambert, Fanny.,Colau, Didier.,...&Lucas, Sophie.(2018).Structural basis of latent TGF-beta 1 presentation and activation by GARP on human regulatory T cells.SCIENCE,362(6417),952-+. |
MLA | Lienart, Stephanie,et al."Structural basis of latent TGF-beta 1 presentation and activation by GARP on human regulatory T cells".SCIENCE 362.6417(2018):952-+. |
条目包含的文件 | 条目无相关文件。 |
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