2K86

Solution Structure of FOXO3a Forkhead domain

2K86 の概要

• エントリーDOI: 10.2210/pdb2k86/pdb
• NMR情報: BMRB: 15939
• 分子名称: Forkhead box protein O3 (1 entity in total)
• 機能のキーワード: forkhead, winged-helix, dna binding domain, activator, apoptosis, chromosomal rearrangement, cytoplasm, dna-binding, nucleus, phosphoprotein, proto-oncogene, transcription, transcription regulation, dna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11706.14

構造登録者

Wang, F.,Marshall, C.B.,Li, G.,Plevin, M.J.,Ikura, M. (登録日: 2008-09-02, 公開日: 2008-10-14, 最終更新日: 2024-05-01)

主引用文献

Wang, F.,Marshall, C.B.,Yamamoto, K.,Li, G.Y.,Plevin, M.J.,You, H.,Mak, T.W.,Ikura, M.
Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53.
J.Mol.Biol., 384:590-603, 2008

PubMed Abstract: FOXO3a, a forkhead transcription factor and member of the forkhead box class O (FOXO) subfamily, has been shown to promote the translocation of p53 to the cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway. However, the binding sites that mediate this interaction between FOXO3a and p53 have not been identified. Here, we show that two regions within FOXO3a, the forkhead (FH) DNA binding domain and a conserved C-terminal transactivation domain (CR3), interact with the DNA binding domain of p53, with affinities in the low millimolar range and low micromolar range, respectively. Our data further suggest that within the FOXO3a molecule, the FH and CR3 domains engage in an intramolecular interaction with low micromolar affinity. Moreover, we used NMR to determine the solution structure of the FH domain. This enabled us to map the binding site for the CR3, which overlaps with the DNA binding site. We demonstrate that an intrinsically disordered linker between the FH and CR3 domains is required for full p53 binding activity. We also show that p53 disrupts the intramolecular interaction between FH and CR3. These results provide evidence for interplay of the FH and CR3 domains in association with p53.

PubMed: 18824006
DOI: 10.1016/j.jmb.2008.09.025

実験手法

SOLUTION NMR