Structural and Biological Features of FOXP3 Dimerization Relevant to Regulatory T Cell Function
文献类型：期刊论文
| 作者 | Song, XM; Li, B; Xiao, Y; Chen, CX; Wang, Q; Liu, YJ; Berezov, A; Xu, C; Gao, YY; Li, ZY |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2012 |
| 卷号 | 1期号:6页码:665-675 |
| 通讯作者 | Zhou, ZC (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,zczhou@sibs.ac.cn ; greene@reo.med.upenn.edu |
| 英文摘要 | FOXP3 is a key transcription factor for regulatory T cell function. We report the crystal structure of the FOXP3 coiled-coil domain, through which a loose or transient dimeric association is formed and modulated, accounting for the activity variations introduced by disease-causing mutations or post-translational modifications. Structure-guided mutagenesis revealed that FOXP3 coiled-coil-mediated homodimerization is essential for Treg function in vitro and in vivo. In particular, we identified human FOXP3 K250 and K252 as key residues for the conformational change and stability of the FOXP3 dimer, which can be regulated by protein posttranslational modifications such as reversible lysine acetylation. These studies provide structural and mechanistic explanations for certain disease-causing mutations in the coiled-coil domain of FOXP3 that are commonly found in IPEX syndrome. Overall, the regulatory machinery involving homooligomerization, acetylation, and heteroassociation has been dissected, defining atomic insights into the biological and pathological characteristics of the FOXP3 complex. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | TRANSCRIPTION FACTOR FOXP3 ; SELF-TOLERANCE ; HISTONE ACETYLTRANSFERASE ; IMMUNE DYSREGULATION ; AUTOIMMUNE-DISEASE ; PROMOTER OCCUPANCY ; GENE-EXPRESSION ; ACETYLATION ; ENTEROPATHY ; PROTEIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000309713100011 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/612]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Song, XM,Li, B,Xiao, Y,et al. Structural and Biological Features of FOXP3 Dimerization Relevant to Regulatory T Cell Function[J]. CELL REPORTS,2012,1(6):665-675. |
| APA | Song, XM.,Li, B.,Xiao, Y.,Chen, CX.,Wang, Q.,...&Greene, MI.(2012).Structural and Biological Features of FOXP3 Dimerization Relevant to Regulatory T Cell Function.CELL REPORTS,1(6),665-675. |
| MLA | Song, XM,et al."Structural and Biological Features of FOXP3 Dimerization Relevant to Regulatory T Cell Function".CELL REPORTS 1.6(2012):665-675. |
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