5yvx | pdb_00005yvx
Crystal structure of SDG8 CW domain in complex with H3K4me1 peptide
Structural highlights
FunctionASHH2_ARATH Histone methyltransferase involved in di and tri-methylation of 'Lys-36' of histone H3 (H3K36me2 and H3K36me3). Binds to H3 already mono- or di-methylated on 'Lys-4'(H3K4me1 or H3K4me2), but not to H3K4me3. H3K4me and H3K36me represent specific tags for epigenetic transcriptional activation. Regulates positively FLC transcription to prevent early flowering transition. Required for flowering transition in response to vernalization and for the maintenance of FLC expression in late embryos, but dispensable for the initial reactivation in early embryos during reprogramming. Seems also to modulate several traits including floral organ size, root size and dormancy. Promotes apical dominance (PubMed:16299497, PubMed:10518493, PubMed:16258034, PubMed:18070919, PubMed:19915673, PubMed:20711170). Directly involved in the tri-methylation of 'Lys-36' of histone H3 (H3K36me3) at LAZ5 chromatin to maintain a transcriptionally active state of LAZ5, a TIR-NB-LRR protein involved in innate immunity (PubMed:20949080).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedChromatin consists of DNA and histones, and specific histone modifications that determine chromatin structure and activity are regulated by three types of proteins, called writer, reader and eraser. Histone reader proteins from vertebrates, vertebrate-infecting parasites, and higher plants possess a CW domain, which has been reported to read histone H3 lysine 4 (H3K4). The CW domain of Arabidopsis SDG8 (also called ASHH2), a histone H3 lysine 36 methyltransferase, preferentially binds monomethylated H3K4 (H3K4me1), unlike the mammalian CW domain protein which binds trimethylated H3K4 (H3K4me3). However, the molecular basis of the selective binding by the SDG8 CW domain (SDG8-CW) remains unclear. Here, we solved the 1.6 A resolution structure of SDG8-CW in complex with H3K4me1, which revealed that residues in the C-terminal alpha helix of SDG8-CW determine binding specificity for low methylation levels at H3K4. Moreover, substitutions of key residues, specifically Ile915 and Asn916, converted SDG8-CW binding preference from H3K4me1 to H3K4me3. Sequence alignments and mutagenesis studies revealed that the CW domain of SDG725, the homolog of SDG8 in rice, shares the same binding preference with SDG8-CW, indicating that preference for low-methylated H3K4 by the CW domain of ASHH2 homologs is conserved among higher-order plants. Our findings provide first structural insights into the molecular basis for specific recognition of monomethylated H3K4 by the H3K4me1 reader protein SDG8 from Arabidopsis. Uncovering the mechanistic basis for specific recognition of monomethylated H3K4 by the CW domain of Arabidopsis histone methyltransferase SDG8.,Liu Y, Huang Y J Biol Chem. 2018 Mar 1. pii: RA117.001390. doi: 10.1074/jbc.RA117.001390. PMID:29496997[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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