5ILS
Autoinhibited ETV1
Summary for 5ILS
| Entry DOI | 10.2210/pdb5ils/pdb |
| Related | 5ILU 5ILV |
| Descriptor | ETS translocation variant 1 (2 entities in total) |
| Functional Keywords | etv1, ets, transcription factor, autoinhibition transcription, dna binding, dna binding protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 11995.81 |
| Authors | Whitby, F.G.,Currie, S.L. (deposition date: 2016-03-04, release date: 2017-02-22, Last modification date: 2024-10-16) |
| Primary citation | Currie, S.L.,Lau, D.K.W.,Doane, J.J.,Whitby, F.G.,Okon, M.,McIntosh, L.P.,Graves, B.J. Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Nucleic Acids Res., 45:2223-2241, 2017 Cited by PubMed Abstract: Autoinhibition enables spatial and temporal regulation of cellular processes by coupling protein activity to surrounding conditions, often via protein partnerships or signaling pathways. We report the molecular basis of DNA-binding autoinhibition of ETS transcription factors ETV1, ETV4 and ETV5, which are often overexpressed in prostate cancer. Inhibitory elements that cooperate to repress DNA binding were identified in regions N- and C-terminal of the ETS domain. Crystal structures of these three factors revealed an α-helix in the C-terminal inhibitory domain that packs against the ETS domain and perturbs the conformation of its DNA-recognition helix. Nuclear magnetic resonance spectroscopy demonstrated that the N-terminal inhibitory domain (NID) is intrinsically disordered, yet utilizes transient intramolecular interactions with the DNA-recognition helix of the ETS domain to mediate autoinhibition. Acetylation of selected lysines within the NID activates DNA binding. This investigation revealed a distinctive mechanism for DNA-binding autoinhibition in the ETV1/4/5 subfamily involving a network of intramolecular interactions not present in other ETS factors. These distinguishing inhibitory elements provide a platform through which cellular triggers, such as protein-protein interactions or post-translational modifications, may specifically regulate the function of these oncogenic proteins. PubMed: 28161714DOI: 10.1093/nar/gkx068 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.399 Å) |
Structure validation
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