7TDW

Structure of FOXP3-DNA complex

7TDW の概要

• エントリーDOI: 10.2210/pdb7tdw/pdb
• 分子名称: Forkhead box P3, DNA (5'-D(*AP*AP*AP*TP*TP*TP*GP*TP*TP*TP*AP*CP*TP*C)-3'), DNA (5'-D(P*GP*AP*GP*TP*AP*AP*AP*CP*AP*AP*AP*TP*TP*T)-3') (3 entities in total)
• 機能のキーワード: foxp3, dimer, forkhead, dna, treg, transcription-dna complex, transcription/dna
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 28757.80

構造登録者

Leng, F.,Hur, S. (登録日: 2022-01-03, 公開日: 2022-08-10, 最終更新日: 2025-12-10)

主引用文献

Leng, F.,Zhang, W.,Ramirez, R.N.,Leon, J.,Zhong, Y.,Hou, L.,Yuki, K.,van der Veeken, J.,Rudensky, A.Y.,Benoist, C.,Hur, S.
The transcription factor FoxP3 can fold into two dimerization states with divergent implications for regulatory T cell function and immune homeostasis.
Immunity, 55:1354-, 2022

PubMed Abstract: FoxP3 is an essential transcription factor (TF) for immunologic homeostasis, but how it utilizes the common forkhead DNA-binding domain (DBD) to perform its unique function remains poorly understood. We here demonstrated that unlike other known forkhead TFs, FoxP3 formed a head-to-head dimer using a unique linker (Runx1-binding region [RBR]) preceding the forkhead domain. Head-to-head dimerization conferred distinct DNA-binding specificity and created a docking site for the cofactor Runx1. RBR was also important for proper folding of the forkhead domain, as truncation of RBR induced domain-swap dimerization of forkhead, which was previously considered the physiological form of FoxP3. Rather, swap-dimerization impaired FoxP3 function, as demonstrated with the disease-causing mutation R337Q, whereas a swap-suppressive mutation largely rescued R337Q-mediated functional impairment. Altogether, our findings suggest that FoxP3 can fold into two distinct dimerization states: head-to-head dimerization representing functional specialization of an ancient DBD and swap dimerization associated with impaired functions.

PubMed: 35926508
DOI: 10.1016/j.immuni.2022.07.002

実験手法

X-RAY DIFFRACTION (4 Å)