2MD5

Structure of uninhibited ETV6 ETS domain

2MD5 の概要

• エントリーDOI: 10.2210/pdb2md5/pdb
• 関連するPDBエントリー: 2LF7 2LF8 4MHG
• NMR情報: BMRB: 19474
• 分子名称: Transcription factor ETV6 (1 entity in total)
• 機能のキーワード: protein, auto-inhibition, transcription
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Nucleus (By similarity): P97360
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12450.35

構造登録者

De, S.,Mcintosh, L.P.,Chan, A.C.,Coyne, H.J.,Okon, M.,Graves, B.J.,Murphy, M.E. (登録日: 2013-08-29, 公開日: 2013-12-25, 最終更新日: 2024-05-15)

主引用文献

De, S.,Chan, A.C.,Coyne, H.J.,Bhachech, N.,Hermsdorf, U.,Okon, M.,Murphy, M.E.,Graves, B.J.,McIntosh, L.P.
Steric Mechanism of Auto-Inhibitory Regulation of Specific and Non-Specific DNA Binding by the ETS Transcriptional Repressor ETV6.
J.Mol.Biol., 426:1390-1406, 2014

PubMed Abstract: DNA binding by the ETS transcriptional repressor ETV6 (or TEL) is auto-inhibited ~50-fold due to an α-helix that sterically blocks its ETS domain binding interface. Using NMR spectroscopy, we demonstrate that this marginally stable helix is unfolded, and not displaced to a non-inhibitory position, when ETV6 is bound to DNA containing a consensus (5')GGAA(3') recognition site. Although significantly lower in affinity, binding to non-specific DNA is auto-inhibited ~5-fold and is also accompanied by helix unfolding. Based on NMR chemical shift perturbations, both specific and non-specific DNA are bound via the same canonical ETS domain interface. However, spectral perturbations are smaller for the non-specific complex, suggesting weaker and less well-defined interactions than in the specific complex. In parallel, the crystal structure of ETV6 bound to a specific DNA duplex was determined. The structure of this complex reveals that a non-conserved histidine residue in the ETS domain recognition helix helps establish the specificity of ETV6 for DNA-binding sites containing (5')GGAA(3')versus(5')GGAT(3'). These studies provide a unified steric mechanism for attenuating ETV6 binding to both specific and non-specific DNA and expand the repertoire of characterized auto-inhibitory strategies utilized to regulate ETS factors.

PubMed: 24333486
DOI: 10.1016/j.jmb.2013.11.031

実験手法

SOLUTION NMR