6VGD

Crystal structure of the DNA binding domain (DBD) of human FLI1 and the complex of the DBD of human Runx2 with core binding factor beta (Cbfb), in complex with 16mer DNA CAGAGGATGTGGCTTC

Summary for 6VGD

• Entry DOI: 10.2210/pdb6vgd/pdb
• Descriptor: 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'), ... (5 entities in total)
• Functional Keywords: ewing sarcoma, enhancer, transcription factor, oncogenesis, prostate cancer, ets-family, runt-family, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 59701.55

Authors

Hou, C.,Tsodikov, O.V. (deposition date: 2020-01-07, release date: 2020-11-25, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (4.2 Å)