7MBN

Cryo-EM structure of MLL1-NCP (H3K4M) complex, mode02

Summary for 7MBN

• Entry DOI: 10.2210/pdb7mbn/pdb
• EMDB information: 23739
• Descriptor: Retinoblastoma-binding protein 5, DNA (146-MER), WD repeat-containing protein 5, ... (10 entities in total)
• Functional Keywords: mll1-ncp, h3k4 methylation, transferase, transferase-dna binding protein-dna complex, transferase/dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 14
• Total formula weight: 377637.06

Authors

Park, S.H.,Ayoub, A.,Lee, Y.T.,Dou, Y.,Cho, U. (deposition date: 2021-04-01, release date: 2021-12-29, Last modification date: 2025-06-04)

Primary citation

Ayoub, A.,Park, S.H.,Lee, Y.T.,Cho, U.S.,Dou, Y.
Regulation of MLL1 Methyltransferase Activity in Two Distinct Nucleosome Binding Modes.
Biochemistry, 61:1-9, 2022

PubMed Abstract: Cryo-EM structures of the KMT2A/MLL1 core complex bound on nucleosome core particles (NCPs) suggest unusual rotational dynamics of the MLL1 complex approaching its physiological substrate. However, the functional implication of such dynamics remains unclear. Here, we show that the MLL1 core complex also shows high rotational dynamics bound on the NCP carrying the catalytically inert histone H3 lysine 4 to methionine (K4M) mutation. There are two major binding modes of the MLL1 complex on the NCP. Importantly, disruption of only one of the binding modes compromised the overall MLL1 activity in an NCP-specific manner. We propose that the MLL1 core complex probably exists in an equilibrium of poised and active binding modes. The high rotational dynamics of the MLL1 complex on the NCP is a feature that can be exploited for loci-specific regulation of H3K4 methylation in higher eukaryotes.

PubMed: 34928138
DOI: 10.1021/acs.biochem.1c00603

Experimental method

ELECTRON MICROSCOPY (4.02 Å)