5ILS

Autoinhibited ETV1

5ILS の概要

• エントリーDOI: 10.2210/pdb5ils/pdb
• 関連するPDBエントリー: 5ILU 5ILV
• 分子名称: ETS translocation variant 1 (2 entities in total)
• 機能のキーワード: etv1, ets, transcription factor, autoinhibition transcription, dna binding, dna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11995.81

構造登録者

Whitby, F.G.,Currie, S.L. (登録日: 2016-03-04, 公開日: 2017-02-22, 最終更新日: 2024-10-16)

主引用文献

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

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: 28161714
DOI: 10.1093/nar/gkx068

実験手法

X-RAY DIFFRACTION (1.399 Å)