3h6z
Crystal Structure of the Four MBT Repeats of Drosophila melanogaster Sfmbt in Complex with Peptide RHR (me)K VLR
Structural highlights
Function[SMBT_DROME] Polycomb group (PcG) protein that binds to the Polycomb response elements (PREs) found in the regulatory regions of many genes. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via the methylation of histones, rendering chromatin heritably changed in its expressibility. Necessary but not sufficient to recruit a functional PcG repressive complex that represses target genes, suggesting that the recruitment of the distinct PRC1 complex is also required to allow a subsequent repression.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPolycomb group (PcG) proteins repress transcription by modifying chromatin structure in target genes. dSfmbt is a subunit of the Drosophila melanogaster PcG protein complex PhoRC and contains four malignant brain tumour (MBT) repeats involved in the recognition of various mono- and dimethylated histone peptides. Here, we present the crystal structure of the four-MBT-repeat domain of dSfmbt in complex with a mono-methylated histone H4 peptide. Only a single histone peptide binds to the four-MBT-repeat domain. Mutational analyses show high-affinity binding with low peptide sequence selectivity through combinatorial interaction of the methyl-lysine with an aromatic cage and positively charged flanking residues with the surrounding negatively charged surface of the fourth MBT repeat. dSfmbt directly interacts with the PcG protein Scm, a related MBT-repeat protein with similar methyl-lysine binding activity. dSfmbt and Scm co-occupy Polycomb response elements of target genes in Drosophila and they strongly synergize in the repression of these target genes, suggesting that the combined action of these two MBT proteins is crucial for Polycomb silencing. Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt.,Grimm C, Matos R, Ly-Hartig N, Steuerwald U, Lindner D, Rybin V, Muller J, Muller CW EMBO J. 2009 Jul 8;28(13):1965-77. Epub 2009 Jun 4. PMID:19494831[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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