2xl2 | pdb_00002xl2
WDR5 IN COMPLEX WITH AN RBBP5 PEPTIDE RECRUITED TO NOVEL SITE
Structural highlights
Function[WDR5_MOUSE] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation (By similarity). [RBBP5_MOUSE] 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. 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. Does not affect ES cell self-renewal. 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 PubMedHistone modification is well established as a fundamental mechanism driving the regulation of transcription, replication and DNA repair through the control of chromatin structure. Likewise, it is apparent that incorrect targeting of histone modifications contributes to misregulated gene expression and hence to developmental disorders and diseases of genomic instability such as cancer. The KMT2 family of SET domain methyltransferases, typified by MLL1, are responsible for histone H3 lysine-4 methylation, a marker of active genes. To ensure that this modification is correctly targeted, a multi-protein complex associates with the methyltransferase and directs activity. We have identified a novel interaction site on the core complex protein WDR5, and mapped the complementary site on its partner RbBP5. We have characterised this interaction by X-ray crystallography and show how it is fundamental to the assembly of the complex and to the regulation of methyltransferase activity. We show which region of RbBP5 contributes directly to MLL activation and combine our structural and biochemical data to produce a model to show how WDR5 and RbBP5 act cooperatively to stimulate activity. Characterisation of a novel WDR5 binding site that recruits RbBP5 through a conserved motif and enhances methylation of H3K4 by MLL1.,Odho Z, Southall SM, Wilson JR J Biol Chem. 2010 Aug 17. PMID:20716525[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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