5VAB

Crystal structure of ATXR5 PHD domain in complex with histone H3

5VAB の概要

• エントリーDOI: 10.2210/pdb5vab/pdb
• 関連するPDBエントリー: 5VA6 5VAC 5VAH
• 分子名称: ATXR5 PHD domain, Histone H3 peptide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: transferase-dna binding protein complex, transferase/dna binding protein
• 由来する生物種: Glycine max (soybean); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7676.62

構造登録者

Bergamin, E.,Sarvan, S.,Malette, J.,Eram, M.,Yeung, S.,Mongeon, V.,Joshi, M.,Brunzelle, J.S.,Michaels, S.D.,Blais, A.,Vedadi, M.,Couture, J.-F. (登録日: 2017-03-24, 公開日: 2017-04-19, 最終更新日: 2023-10-04)

主引用文献

Bergamin, E.,Sarvan, S.,Malette, J.,Eram, M.S.,Yeung, S.,Mongeon, V.,Joshi, M.,Brunzelle, J.S.,Michaels, S.D.,Blais, A.,Vedadi, M.,Couture, J.F.
Molecular basis for the methylation specificity of ATXR5 for histone H3.
Nucleic Acids Res., 45:6375-6387, 2017

PubMed Abstract: In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases ARABIDOPSIS TRITHORAX RELATED PROTEIN 5 and 6 (ATXR5/6) regulate heterochromatic DNA replication and genome stability. Our initial studies showed that ATXR5/6 discriminate between histone H3 variants and preferentially methylate K27 on H3.1. In this study, we report three regulatory mechanisms contributing to the specificity of ATXR5/6. First, we show that ATXR5 preferentially methylates the R/F-K*-S/C-G/A-P/C motif with striking preference for hydrophobic and aromatic residues in positions flanking this core of five amino acids. Second, we demonstrate that post-transcriptional modifications of residues neighboring K27 that are typically associated with actively transcribed chromatin are detrimental to ATXR5 activity. Third, we show that ATXR5 PHD domain employs a narrow binding pocket to selectively recognize unmethylated K4 of histone H3. Finally, we demonstrate that deletion or mutation of the PHD domain reduces the catalytic efficiency (kcat/Km of AdoMet) of ATXR5 up to 58-fold, highlighting the multifunctional nature of ATXR5 PHD domain. Overall, our results suggest that several molecular determinants regulate ATXR5/6 methyltransferase activity and epigenetic inheritance of H3.1 K27me1 mark in plants.

PubMed: 28383693
DOI: 10.1093/nar/gkx224

実験手法

X-RAY DIFFRACTION (1.702 Å)