6w5m

Cryo-EM structure of MLL1 in complex with RbBP5, WDR5, SET1, and ASH2L bound to the nucleosome (Class02)

spinqualitylabelsall models 6w5m, resolution 4.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6w5m is a 14 chain structure with sequence from Homo sapiens, Xenopus laevis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.6Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RBBP5_HUMAN In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Publication Abstract from PubMed Recent cryo-EM structures show the highly dynamic nature of the MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation of such dynamics remain unclear. Here we show that DPY30 and the intrinsically disordered regions (IDRs) of ASH2L work together in restricting the rotational dynamics of the MLL1 complex on the NCP. We show that DPY30 binding to ASH2L leads to stabilization and integration of ASH2L IDRs into the MLL1 complex and establishes new ASH2L-NCP contacts. The significance of ASH2L-DPY30 interactions is demonstrated by requirement of both ASH2L IDRs and DPY30 for dramatic increase of processivity and activity of the MLL1 complex. This DPY30 and ASH2L-IDR dependent regulation is NCP-specific and applies to all members of the MLL/SET1 family of enzymes. We further show that DPY30 is causal for de novo establishment of H3K4me3 in ESCs. Our study provides a paradigm of how H3K4me3 is regulated on chromatin and how H3K4me3 heterogeneity can be modulated by ASH2L IDR interacting proteins. Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin.,Lee YT, Ayoub A, Park SH, Sha L, Xu J, Mao F, Zheng W, Zhang Y, Cho US, Dou Y Nat Commun. 2021 May 19;12(1):2953. doi: 10.1038/s41467-021-23268-9. PMID:34012049 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures Histone methyltransferase 3D structures Retinoblastoma-binding protein 3D structures WD-repeat protein 3D structures

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