7UD5

Complex between MLL1-WRAD and an H2B-ubiquitinated nucleosome

7UD5 の概要

• エントリーDOI: 10.2210/pdb7ud5/pdb
• EMDBエントリー: 26454
• 分子名称: Histone H3, Retinoblastoma-binding protein 5, Polyubiquitin-B, ... (14 entities in total)
• 機能のキーワード: ubiquitin, chromatin, mll, methylation, dna binding protein
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 17
• 化学式量合計: 414653.38

構造登録者

Niklas, H.A.,Rahman, S.,Worden, E.J.,Wolberger, C. (登録日: 2022-03-18, 公開日: 2022-09-21, 最終更新日: 2024-12-25)

主引用文献

Rahman, S.,Hoffmann, N.A.,Worden, E.J.,Smith, M.L.,Namitz, K.E.W.,Knutson, B.A.,Cosgrove, M.S.,Wolberger, C.
Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome.
Proc.Natl.Acad.Sci.USA, 119:e2205691119-e2205691119, 2022

PubMed Abstract: The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, DR5, bBp5, sh2L, and PY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex.

PubMed: 36095189
DOI: 10.1073/pnas.2205691119

実験手法

ELECTRON MICROSCOPY (4.25 Å)