6KIV

Cryo-EM structure of human MLL1-ubNCP complex (4.0 angstrom)

6KIV の概要

• エントリーDOI: 10.2210/pdb6kiv/pdb
• EMDBエントリー: 9999
• 分子名称: Histone H3, Set1/Ash2 histone methyltransferase complex subunit ASH2, WD repeat-containing protein 5, ... (13 entities in total)
• 機能のキーワード: histone modification, nucleosome, mll, transcription, transcription-dna complex, transcription/dna
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 387793.20

構造登録者

Huang, J.,Xue, H.,Yao, T. (登録日: 2019-07-20, 公開日: 2019-09-11, 最終更新日: 2024-03-27)

主引用文献

Xue, H.,Yao, T.,Cao, M.,Zhu, G.,Li, Y.,Yuan, G.,Chen, Y.,Lei, M.,Huang, J.
Structural basis of nucleosome recognition and modification by MLL methyltransferases.
Nature, 573:445-449, 2019

PubMed Abstract: Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification.

PubMed: 31485071
DOI: 10.1038/s41586-019-1528-1

実験手法

ELECTRON MICROSCOPY (4 Å)