2LF7

Intramolecular regulation of the ETS Domain within ETV6 sequence R335 to Q436

2LF7 の概要

• エントリーDOI: 10.2210/pdb2lf7/pdb
• 関連するPDBエントリー: 2LF8
• NMR情報: BMRB: 17741
• 分子名称: Transcription factor ETV6 (1 entity in total)
• 機能のキーワード: 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: 13060.99

構造登録者

Coyne III, H.,Green, S.M.,Graves, B.J.,Mcintosh, L.P. (登録日: 2011-06-28, 公開日: 2012-05-23, 最終更新日: 2024-05-15)

主引用文献

Coyne, H.J.,De, S.,Okon, M.,Green, S.M.,Bhachech, N.,Graves, B.J.,McIntosh, L.P.
Autoinhibition of ETV6 (TEL) DNA Binding: Appended Helices Sterically Block the ETS Domain.
J.Mol.Biol., 421:67-84, 2012

PubMed Abstract: ETV6 (or TEL), a transcriptional repressor belonging to the ETS family, is frequently involved in chromosomal translocations linked with human cancers. It displays a DNA-binding mode distinct from other ETS proteins due to the presence of a self-associating PNT domain. In this study, we used NMR spectroscopy to dissect the structural and dynamic bases for the autoinhibition of ETV6 DNA binding by sequences C-terminal to its ETS domain. The C-terminal inhibitory domain (CID) contains two helices, H4 and H5, which sterically block the DNA-binding interface of the ETS domain. Importantly, these appended helices are only marginally stable as revealed by amide hydrogen exchange and (15)N relaxation measurements. The CID is thus poised to undergo a facile conformational change as required for DNA binding. The CID also dampens millisecond timescale motions of the ETS domain hypothesized to be critical for the recognition of specific ETS target sequences. This work illustrates the use of appended sequences on conserved structural domains to generate biological diversity and complements previous studies of the allosteric mechanism of ETS1 autoinhibition to reveal both common and divergent features underlying the regulation of DNA binding by ETS transcription factors.

PubMed: 22584210
DOI: 10.1016/j.jmb.2012.05.010

実験手法

SOLUTION NMR