9MX8

Crystal structure of the DNA binding domain of FLI1 in complex with a DNA containing three contiguous GGAA sites

9MX8 の概要

• エントリーDOI: 10.2210/pdb9mx8/pdb
• 関連するPDBエントリー: 9MWY
• 分子名称: Friend leukemia integration 1 transcription factor, DNA (5'-D(P*GP*AP*CP*CP*GP*GP*AP*AP*GP*GP*AP*AP*GP*GP*AP*AP*GP*TP*G)-3'), DNA (5'-D(*CP*AP*CP*TP*TP*CP*CP*TP*TP*CP*CP*TP*TP*CP*CP*GP*GP*TP*C)-3') (3 entities in total)
• 機能のキーワード: oncogene, ewing sarcoma, transcription factor, microsatellite, dna binding protein-dna complex, dna binding protein, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 53239.29

構造登録者

Hou, C.,Tsodikov, O.V. (登録日: 2025-01-17, 公開日: 2025-03-12, 最終更新日: 2025-04-23)

主引用文献

Hou, C.,Tsodikov, O.V.
Structure and cooperative formation of a FLI1 filament on contiguous GGAA DNA sites.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: Ewing sarcoma, a pediatric cancer of bone and soft tissue, is driven in most cases by an abnormal oncogenic fusion of the N-terminal region of EWS with the C-terminal region of FLI1 (EWS-FLI1). The FLI1 region contains a conserved DNA-binding domain (DBD) essential for the oncogenesis. Binding of EWS-FLI1 to microsatellites composed of contiguous GGAA sites, shown previously to be critical for the oncogenic program of this fusion, is not well understood. In this study, we demonstrate that the FLI1 DBD binds cooperatively to contiguous GGAA sites, thereby forming a nucleoprotein filament. A series of crystal structures of two, three, and four FLI1 DBD proteins in complexes with DNA oligomers containing two, three, and four contiguous GGAA sites, respectively, reveal the structure of this filament and the basis for its cooperative formation. We expect this mechanistic insight to be an important milestone in our understanding of the oncogenic function of EWS-FLI1 and exploiting it as a drug target.

PubMed: 40131773
DOI: 10.1093/nar/gkaf205

実験手法

X-RAY DIFFRACTION (3.15 Å)