6U81

Crystal Structure of the Double Homeodomain of DUX4 in Complex with a DNA aptamer

6U81 の概要

• エントリーDOI: 10.2210/pdb6u81/pdb
• 分子名称: Double homeobox protein 4, DNA (5'-D(*GP*CP*GP*TP*AP*AP*TP*CP*TP*AP*AP*TP*CP*AP*AP*CP*A)-3'), DNA (5'-D(*TP*GP*TP*TP*GP*AP*TP*TP*AP*GP*CP*CP*CP*AP*TP*TP*AP*CP*GP*C)-3'), ... (5 entities in total)
• 機能のキーワード: dux tandem homeodomains, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 27033.31

構造登録者

Shi, K.,Aihara, H. (登録日: 2019-09-04, 公開日: 2020-02-19, 最終更新日: 2023-10-11)

主引用文献

Klingler, C.,Ashley, J.,Shi, K.,Stiefvater, A.,Kyba, M.,Sinnreich, M.,Aihara, H.,Kinter, J.
DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD.
Faseb J., 34:4573-4590, 2020

PubMed Abstract: Aberrant expression of the transcription factor double homeobox protein 4 (DUX4) can lead to a number of diseases including facio-scapulo-humeral muscular dystrophy (FSHD), acute lymphoblastic leukemia, and sarcomas. Inhibition of DUX4 may represent a therapeutic strategy for these diseases. By applying Systematic Evolution of Ligands by EXponential Enrichment (SELEX), we identified aptamers against DUX4 with specific secondary structural elements conveying high affinity to DUX4 as assessed by fluorescence resonance energy transfer and fluorescence polarization techniques. Sequences analysis of these aptamers revealed the presence of two consensus DUX4 motifs in a reverse complementary fashion forming hairpins interspersed with bulge loops at distinct positions that enlarged the binding surface with the DUX4 protein, as determined by crystal structure analysis. We demonstrate that insertion of specific structural elements into transcription factor binding oligonucleotides can enhance specificity and affinity.

PubMed: 32020675
DOI: 10.1096/fj.201902696

実験手法

X-RAY DIFFRACTION (2.34 Å)