6o7g

Solution structure of MLL4 PHD6 domain in complex with histone H4K16ac peptide

spinqualitylabelsall models 6o7g Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6o7g is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: ACE, ALY, NH2, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease KMT2D_HUMAN Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function KMT2D_HUMAN Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription. Publication Abstract from PubMed Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we identify the PHD6 finger of MLL4 (MLL4-PHD6) as a selective reader of the epigenetic modification H4K16ac. The solution NMR structure of MLL4-PHD6 in complex with a H4K16ac peptide along with binding and mutational analyses reveal unique mechanistic features underlying recognition of H4K16ac. Genomic studies show that one third of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions in vivo and that MLL4 occupancy in a set of genomic targets depends on the acetyltransferase activity of MOF, a H4K16ac-specific acetyltransferase. The recognition of H4K16ac is conserved in the PHD7 finger of paralogous MLL3. Together, our findings reveal a previously uncharacterized acetyllysine reader and suggest that selective targeting of H4K16ac by MLL4 provides a direct functional link between MLL4, MOF and H4K16 acetylation. Selective binding of the PHD6 finger of MLL4 to histone H4K16ac links MLL4 and MOF.,Zhang Y, Jang Y, Lee JE, Ahn J, Xu L, Holden MR, Cornett EM, Krajewski K, Klein BJ, Wang SP, Dou Y, Roeder RG, Strahl BD, Rothbart SB, Shi X, Ge K, Kutateladze TG Nat Commun. 2019 May 24;10(1):2314. doi: 10.1038/s41467-019-10324-8. PMID:31127101 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures Histone methyltransferase 3D structures

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