4IX7

Crystal Structure of the insv-BEN domain complexed to its DNA target site

4IX7 の概要

• エントリーDOI: 10.2210/pdb4ix7/pdb
• 分子名称: 5'-D(*GP*TP*TP*CP*CP*AP*AP*TP*TP*GP*GP*AP*A)-3', RE55538p (3 entities in total)
• 機能のキーワード: ben domain, transcriptional repressor, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 34090.25

構造登録者

Ren, A.,Serganov, A.,Patel, D.J. (登録日: 2013-01-24, 公開日: 2013-03-20, 最終更新日: 2024-10-30)

主引用文献

Dai, Q.,Ren, A.,Westholm, J.O.,Serganov, A.A.,Patel, D.J.,Lai, E.C.
The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
Genes Dev., 27:602-614, 2013

PubMed Abstract: We recently reported that Drosophila Insensitive (Insv) promotes sensory organ development and has activity as a nuclear corepressor for the Notch transcription factor Suppressor of Hairless [Su(H)]. Insv lacks domains of known biochemical function but contains a single BEN domain (i.e., a "BEN-solo" protein). Our chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) analysis confirmed binding of Insensitive to Su(H) target genes in the Enhancer of split gene complex [E(spl)-C]; however, de novo motif analysis revealed a novel site strongly enriched in Insv peaks (TCYAATHRGAA). We validate binding of endogenous Insv to genomic regions bearing such sites, whose associated genes are enriched for neural functions and are functionally repressed by Insv. Unexpectedly, we found that the Insv BEN domain binds specifically to this sequence motif and that Insv directly regulates transcription via this motif. We determined the crystal structure of the BEN-DNA target complex, revealing homodimeric binding of the BEN domain and extensive nucleotide contacts via α helices and a C-terminal loop. Point mutations in key DNA-contacting residues severely impair DNA binding in vitro and capacity for transcriptional regulation in vivo. We further demonstrate DNA-binding and repression activities by the mammalian neural BEN-solo protein BEND5. Altogether, we define novel DNA-binding activity in a conserved family of transcriptional repressors, opening a molecular window on this extensive gene family.

PubMed: 23468431
DOI: 10.1101/gad.213314.113

実験手法

X-RAY DIFFRACTION (1.581 Å)