9CP6
Crystal structure of the DNA binding domain of FLI1 (residues 259-371)
Summary for 9CP6
| Entry DOI | 10.2210/pdb9cp6/pdb |
| Descriptor | Friend leukemia integration 1 transcription factor, SODIUM ION (3 entities in total) |
| Functional Keywords | transcription factor, ewing sarcoma, ets family, dna binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13496.19 |
| Authors | Hou, C.,Tsodikov, O.V. (deposition date: 2024-07-17, release date: 2025-03-12, Last modification date: 2025-04-09) |
| Primary citation | Hou, C.,Tsodikov, O.V. Structure and cooperative formation of a FLI1 filament on contiguous GGAA DNA sites. Nucleic Acids Res., 53:-, 2025 Cited by 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: 40131773DOI: 10.1093/nar/gkaf205 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.66 Å) |
Structure validation
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