4MZF

Crystal structure of human Spindlin1 bound to histone H3(K4me3-R8me2a) peptide

4MZF の概要

• エントリーDOI: 10.2210/pdb4mzf/pdb
• 関連するPDBエントリー: 4MZG 4MZH
• 分子名称: Peptide from Histone H3.2, Spindlin-1, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: wnt signal, histone h3, nuclear, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q71DI3 Q9Y657
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26837.35

構造登録者

Su, X.,Ding, X.,Li, H. (登録日: 2013-09-30, 公開日: 2014-03-26, 最終更新日: 2025-03-26)

主引用文献

Su, X.,Zhu, G.,Ding, X.,Lee, S.Y.,Dou, Y.,Zhu, B.,Wu, W.,Li, H.
Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1
Genes Dev., 28:622-636, 2014

PubMed Abstract: Histone modification patterns and their combinatorial readout have emerged as a fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1 as a histone effector that senses a cis-tail histone H3 methylation pattern involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8 (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats. Cocrystal structure determination established concurrent recognition of H3K4me3 and H3R8me2a by Spin/Ssty repeats 2 and 1, respectively. Both H3K4me3 and H3R8me2a are recognized using an "insertion cavity" recognition mode, contributing to a methylation state-specific layer of regulation. In vivo functional studies suggest that Spindlin1 activates Wnt/β-catenin signaling downstream from protein arginine methyltransferase 2 (PRMT2) and the MLL complex, which together are capable of generating a specific H3 "K4me3-R8me2a" pattern. Mutagenesis of Spindlin1 reader pockets impairs activation of Wnt target genes. Taken together, our work connects a histone "lysine-arginine" methylation pattern readout by Spindlin1-to-Wnt signaling at the transcriptional level.

PubMed: 24589551
DOI: 10.1101/gad.233239.113

実験手法

X-RAY DIFFRACTION (2.098 Å)