3QRF

Structure of a domain-swapped FOXP3 dimer

3QRF の概要

• エントリーDOI: 10.2210/pdb3qrf/pdb
• 関連するPDBエントリー: 1a02 1owr 2a07 2as5
• 分子名称: Nuclear factor of activated T-cells, cytoplasmic 2, Forkhead box protein P3, human hARRE2 DNA (Plus Strand), ... (6 entities in total)
• 機能のキーワード: beta barrel, domain swap, forkhead domain, immnoglobulin fold, protein-dna complex, double helix, transcription regulation, dna binding, nucleus, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q13469; Nucleus : Q9BZS1
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 130608.36

構造登録者

Bandukwala, H.S.,Wu, Y.,Feurer, M.,Chen, Y.,Barbosa, B.,Ghosh, S.,Stroud, J.C.,Benoist, C.,Mathis, D.,Rao, A.,Chen, L. (登録日: 2011-02-17, 公開日: 2011-04-20, 最終更新日: 2023-09-13)

主引用文献

Bandukwala, H.S.,Wu, Y.,Feuerer, M.,Chen, Y.,Barboza, B.,Ghosh, S.,Stroud, J.C.,Benoist, C.,Mathis, D.,Rao, A.,Chen, L.
Structure of a Domain-Swapped FOXP3 Dimer on DNA and Its Function in Regulatory T Cells.
Immunity, 34:479-491, 2011

PubMed Abstract: The transcription factor FOXP3 is essential for the suppressive function of regulatory T cells that are required for maintaining self-tolerance. We have solved the crystal structure of the FOXP3 forkhead domain as a ternary complex with the DNA-binding domain of the transcription factor NFAT1 and a DNA oligonucleotide from the interleukin-2 promoter. A striking feature of this structure is that FOXP3 forms a domain-swapped dimer that bridges two molecules of DNA. Structure-guided or autoimmune disease (IPEX)-associated mutations in the domain-swap interface diminished dimer formation by the FOXP3 forkhead domain without compromising FOXP3 DNA binding. These mutations also eliminated T cell-suppressive activity conferred by FOXP3, both in vitro and in a murine model of autoimmune diabetes in vivo. We conclude that FOXP3-mediated suppressor function requires dimerization through the forkhead domain and that mutations in the dimer interface can lead to the systemic autoimmunity observed in IPEX patients.

PubMed: 21458306
DOI: 10.1016/j.immuni.2011.02.017

実験手法

X-RAY DIFFRACTION (2.8 Å)