3U2B

Structure of the Sox4 HMG domain bound to DNA

3U2B の概要

• エントリーDOI: 10.2210/pdb3u2b/pdb
• 関連するPDBエントリー: 1gt0 3f27
• 分子名称: DNA (5'-D(*GP*TP*CP*TP*CP*TP*AP*TP*TP*GP*TP*CP*CP*TP*GP*G)-3'), DNA (5'-D(*CP*CP*AP*GP*GP*AP*CP*AP*AP*TP*AP*GP*AP*GP*AP*C)-3'), Transcription factor SOX-4, ... (4 entities in total)
• 機能のキーワード: hmg domain, transcriptional regulation, transcription-dna complex, transcription/dna
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Nucleus: Q06831
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 19514.90

構造登録者

Jauch, R.,Ng, C.K.L.,Kolatkar, P.R. (登録日: 2011-10-03, 公開日: 2011-12-28, 最終更新日: 2024-03-20)

主引用文献

Jauch, R.,Ng, C.K.L.,Narasimhan, K.,Kolatkar, P.R.
The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition
Biochem.J., 443:39-47, 2012

PubMed Abstract: It has recently been proposed that the sequence preferences of DNA-binding TFs (transcription factors) can be well described by models that include the positional interdependence of the nucleotides of the target sites. Such binding models allow for multiple motifs to be invoked, such as principal and secondary motifs differing at two or more nucleotide positions. However, the structural mechanisms underlying the accommodation of such variant motifs by TFs remain elusive. In the present study we examine the crystal structure of the HMG (high-mobility group) domain of Sox4 [Sry (sex-determining region on the Y chromosome)-related HMG box 4] bound to DNA. By comparing this structure with previously solved structures of Sox17 and Sox2, we observed subtle conformational differences at the DNA-binding interface. Furthermore, using quantitative electrophoretic mobility-shift assays we validated the positional interdependence of two nucleotides and the presence of a secondary Sox motif in the affinity landscape of Sox4. These results suggest that a concerted rearrangement of two interface amino acids enables Sox4 to accommodate primary and secondary motifs. The structural adaptations lead to altered dinucleotide preferences that mutually reinforce each other. These analyses underline the complexity of the DNA recognition by TFs and provide an experimental validation for the conceptual framework of positional interdependence and secondary binding motifs.

PubMed: 22181698
DOI: 10.1042/BJ20111768

実験手法

X-RAY DIFFRACTION (2.402 Å)