8PNA

transcription factor BARHL2 bound to TAATG DNA sequence

8PNA の概要

• エントリーDOI: 10.2210/pdb8pna/pdb
• 関連するPDBエントリー: 8PM5 8PM7 8PMC 8PMF 8PMN 8PMV 8PN4
• 分子名称: DNA, BarH-like 2 homeobox protein, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: homeobox transcription factor, barhl2, dna-binding domain, protein-dna complex, transcription
• 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: 15479.10

構造登録者

Morgunova, E.,Popov, A.,Yin, Y.,Taipale, J. (登録日: 2023-06-30, 公開日: 2024-07-10, 最終更新日: 2025-01-15)

主引用文献

Morgunova, E.,Nagy, G.,Yin, Y.,Zhu, F.,Nayak, S.P.,Xiao, T.,Sokolov, I.,Popov, A.,Laughton, C.,Grubmuller, H.,Taipale, J.
Interfacial water confers transcription factors with dinucleotide specificity.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins. The dinucleotides were recognized either enthalpically, by an extensive water network that connects the adjacent bases to the TF, or entropically, by a hydrophobic patch that maintained interfacial water mobility. This mechanism confers differential temperature sensitivity to the optimal sites, with implications for thermal regulation of gene expression. Our results uncover the enigma of how TFs can recognize more complex local features than mononucleotides and demonstrate that water-mediated recognition is important for predicting affinities of macromolecules from their sequence.

PubMed: 39753777
DOI: 10.1038/s41594-024-01449-6

実験手法

X-RAY DIFFRACTION (1.45 Å)