EMD-20512

Single-particle
6.2 Å
EMD-20512 Deposition: 23/07/2019
Map released: 18/12/2019
Last modified: 16/08/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-20512

Cryo-EM structure of MLL1 in complex with RbBP5 and WDR5 bound to the nucleosome

EMD-20512

Single-particle
6.2 Å
EMD-20512 Deposition: 23/07/2019
Map released: 18/12/2019
Last modified: 16/08/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Xenopus laevis, Homo sapiens, synthetic construct
Sample: Human MLL1 complex bound to the nucleosome
Fitted models: 6pwv (Avg. Q-score: 0.188)

Deposition Authors: Park SH , Ayoub A
Cryo-EM structure of the human MLL1 core complex bound to the nucleosome.
Park SH , Ayoub A, Lee YT , Xu J, Kim H , Zheng W , Zhang B, Sha L , An S, Zhang Y, Cianfrocco MA , Su M, Dou Y , Cho US
(2019) Nat Commun , 10 , 5540 - 5540
PUBMED: 31804488
DOI: doi:10.1038/s41467-019-13550-2
ISSN: 2041-1723
Abstract:
Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1SET domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.