6VG8

Crystal structure of the DNA binding domains of human FLI1 and Runx2 in complex with 16-mer DNA CAGAGGATGTGGCTTC

6VG8 の概要

• エントリーDOI: 10.2210/pdb6vg8/pdb
• 分子名称: Friend leukemia integration 1 transcription factor, DNA (5'-D(P*CP*AP*GP*AP*GP*GP*AP*TP*GP*TP*GP*GP*CP*TP*TP*C)-3'), DNA (5'-D(P*GP*AP*AP*GP*CP*CP*AP*CP*AP*TP*CP*CP*TP*CP*TP*G)-3'), ... (4 entities in total)
• 機能のキーワード: oncogenesis, ewing sarcoma, enhancer, bone cancer, leukemia, ets-family, runt-family, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 35597.69

構造登録者

Hou, C.,Tsodikov, O.V. (登録日: 2020-01-07, 公開日: 2020-11-25, 最終更新日: 2023-10-11)

主引用文献

Hou, C.,Mandal, A.,Rohr, J.,Tsodikov, O.V.
Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins.
Structure, 29:404-412.e4, 2021

PubMed Abstract: ETS family transcription factors of ERG and FLI1 play a key role in oncogenesis of prostate cancer and Ewing sarcoma by binding regulatory DNA sites and interfering with function of other factors. Mithramycin (MTM) is an anti-cancer, DNA binding natural product that functions as a potent antagonist of ERG and FLI1 by an unknown mechanism. We present a series of crystal structures of the DNA binding domain (DBD) of ERG/FLI1 culminating in a structure of a high-order complex of the ERG/FLI1 DBD, transcription factor Runx2, core-binding factor beta (Cbfβ), and MTM on a DNA enhancer site, along with supporting DNA binding studies using MTM and its analogues. Taken together, these data provide insight into allosteric mechanisms underlying ERG and FLI1 transactions and their disruption by MTM analogues.

PubMed: 33275876
DOI: 10.1016/j.str.2020.11.012

実験手法

X-RAY DIFFRACTION (4.31 Å)