6QVW

Solution structure of the free FOXO1 DNA binding domain

6QVW の概要

• エントリーDOI: 10.2210/pdb6qvw/pdb
• 分子名称: Forkhead box protein O1 (1 entity in total)
• 機能のキーワード: foxo1, trasncription factor, dna binding, transcription
• 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: 13214.92

構造登録者

Psenakova, K.,Obsil, T.,Veverka, V.,Obsilova, V.,Kohoutova, K. (登録日: 2019-03-05, 公開日: 2019-09-04, 最終更新日: 2024-06-19)

主引用文献

Psenakova, K.,Kohoutova, K.,Obsilova, V.,Ausserlechner, M.J.,Veverka, V.,Obsil, T.
Forkhead Domains of FOXO Transcription Factors Differ in both Overall Conformation and Dynamics.
Cells, 8:-, 2019

PubMed Abstract: FOXO transcription factors regulate cellular homeostasis, longevity and response to stress. FOXO1 (also known as FKHR) is a key regulator of hepatic glucose production and lipid metabolism, and its specific inhibition may have beneficial effects on diabetic hyperglycemia by reducing hepatic glucose production. Moreover, all FOXO proteins are considered potential drug targets for drug resistance prevention in cancer therapy. However, the development of specific FOXO inhibitors requires a detailed understanding of structural differences between individual FOXO DNA-binding domains. The high-resolution structure of the DNA-binding domain of FOXO1 reported in this study and its comparison with structures of other FOXO proteins revealed differences in both their conformation and flexibility. These differences are encoded by variations in protein sequences and account for the distinct functions of FOXO proteins. In particular, the positions of the helices H1, H2 and H3, whose interface form the hydrophobic core of the Forkhead domain, and the interactions between hydrophobic residues located on the interface between the N-terminal segment, the H2-H3 loop, and the recognition helix H3 differ among apo FOXO1, FOXO3 and FOXO4 proteins. Therefore, the availability of apo structures of DNA-binding domains of all three major FOXO proteins will support the development of FOXO-type-specific inhibitors.

PubMed: 31450545
DOI: 10.3390/cells8090966

実験手法

SOLUTION NMR