4riq | pdb_00004riq
Crystal structure of DPY-30 dimerization/docking domain in complex with Ash2L Sdc1-DPY-30 Interacting region (SDI)
Structural highlights
Function[DPY30_HUMAN] As part of the MLL1/MLL complex, involved in the methylation of histone H3 at 'Lys-4', particularly trimethylation. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In a teratocarcinoma cell, plays a crucial role in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci. May also play an indirect or direct role in endosomal transport.[1] [2] [3] [ASH2L_HUMAN] Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. May function as a transcriptional regulator. May play a role in hematopoiesis.[4] [5] Publication Abstract from PubMedDPY-30 is a subunit of mammalian COMPASS-like complexes (complex of proteins associated with Set1) and regulates global histone H3 Lys-4 trimethylation. Here we report structural evidence showing that the incorporation of DPY-30 into COMPASS-like complexes is mediated by several hydrophobic interactions between an amphipathic alpha helix located on the C terminus of COMPASS subunit ASH2L and the inner surface of the DPY-30 dimerization/docking (D/D) module. Mutations impairing the interaction between ASH2L and DPY-30 result in a loss of histone H3K4me3 at the beta locus control region and cause a delay in erythroid cell terminal differentiation. Using overlay assays, we defined a consensus sequence for DPY-30 binding proteins and found that DPY-30 interacts with BAP18, a subunit of the nucleosome remodeling factor complex. Overall, our results indicate that the ASH2L/DPY-30 complex is important for cell differentiation and provide insights into the ability of DPY-30 to associate with functionally divergent multisubunit complexes. Molecular Basis for DPY-30 Association to COMPASS-like and NURF Complexes.,Tremblay V, Zhang P, Chaturvedi CP, Thornton J, Brunzelle JS, Skiniotis G, Shilatifard A, Brand M, Couture JF Structure. 2014 Dec 2;22(12):1821-30. doi: 10.1016/j.str.2014.10.002. Epub 2014, Nov 20. PMID:25456412[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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