7W6L

The crystal structure of MLL3-RBBP5-ASH2L in complex with H3K4me0 peptide

7W6L の概要

• エントリーDOI: 10.2210/pdb7w6l/pdb
• 分子名称: Set1/Ash2 histone methyltransferase complex subunit ASH2, Histone-lysine N-methyltransferase 2C, Retinoblastoma-binding protein 5, ... (7 entities in total)
• 機能のキーワード: mll family methyltransferases, product specificity, f/y switch, protein binding, protein binding-transferase complex, protein binding/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 86552.41

構造登録者

Zhao, L.,Li, Y.,Chen, Y. (登録日: 2021-12-01, 公開日: 2022-09-07, 最終更新日: 2023-11-29)

主引用文献

Li, Y.,Zhao, L.,Zhang, Y.,Wu, P.,Xu, Y.,Mencius, J.,Zheng, Y.,Wang, X.,Xu, W.,Huang, N.,Ye, X.,Lei, M.,Shi, P.,Tian, C.,Peng, C.,Li, G.,Liu, Z.,Quan, S.,Chen, Y.
Structural basis for product specificities of MLL family methyltransferases.
Mol.Cell, 82:3810-3825.e8, 2022

PubMed Abstract: Human mixed-lineage leukemia (MLL) family methyltransferases methylate histone H3 lysine 4 to different methylation states (me1/me2/me3) with distinct functional outputs, but the mechanism underlying the different product specificities of MLL proteins remains unclear. Here, we develop methodologies to quantitatively measure the methylation rate difference between mono-, di-, and tri-methylation steps and demonstrate that MLL proteins possess distinct product specificities in the context of the minimum MLL-RBBP5-ASH2L complex. Comparative structural analyses of MLL complexes by X-ray crystal structures, fluorine-19 nuclear magnetic resonance, and molecular dynamics simulations reveal that the dynamics of two conserved tyrosine residues at the "F/Y (phenylalanine/tyrosine) switch" positions fine-tune the product specificity. The variation in the intramolecular interaction between SET-N and SET-C affects the F/Y switch dynamics, thus determining the product specificities of MLL proteins. These results indicate a modified F/Y switch rule applicable for most SET domain methyltransferases and implicate the functional divergence of MLL proteins.

PubMed: 36108631
DOI: 10.1016/j.molcel.2022.08.022

実験手法

X-RAY DIFFRACTION (2.26 Å)