Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex Journal Article
| Authors: | Ruthenburg, A. J.; Wang, W.; Graybosch, D. M.; Li, H.; Allis, C. D.; Patel, D. J.; Verdine, G. L. |
| Article Title: | Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex |
| Abstract: | WDR5 is a core component of SET1-family complexes that achieve transcriptional activation via methylation of histone H3 on Nζ of Lys4 (H3K4). The role of WDR5 in the MLL1 complex has recently been described as specific recognition of dimethyl-K4 in the context of a histone H3 amino terminus; WDR5 is essential for vertebrate development, Hox gene activation and global H3K4 trimethylation. We report the high-resolution X-ray structures of WDR5 in the unliganded form and complexed with histone H3 peptides having unmodified and mono-, di- and trimethylated K4, which together provide the first comprehensive analysis of methylated histone recognition by the ubiquitous WD40-repeat fold. Contrary to predictions, the structures reveal that WDR5 does not read out the methylation state of K4 directly, but instead serves to present the K4 side chain for further methylation by SET1-family complexes. © 2006 Nature Publishing Group. |
| Keywords: | controlled study; unclassified drug; methylation; protein conformation; protein function; protein analysis; protein protein interaction; transcription initiation; protein; protein binding; protein interaction; peptide; vertebrata; gene activation; amino acid sequence; molecular sequence data; amino terminal sequence; molecular recognition; histone h3; peptides; models, molecular; crystallography, x-ray; multiprotein complexes; binding sites; development; protein subunit; protein folding; protein structure; protein family; vertebrate; histones; aspartic acid; lysine; protein methylation; protein modification; tryptophan; x ray analysis; mixed lineage leukemia protein; myeloid-lymphoid leukemia protein; hox gene; protein wdr5; mixed lineage leukemia protein 1; protein set1; heterotrimeric gtp-binding proteins |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 13 |
| Issue: | 8 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2006-08-01 |
| Start Page: | 704 |
| End Page: | 712 |
| Language: | English |
| DOI: | 10.1038/nsmb1119 |
| PUBMED: | 16829959 |
| PROVIDER: | scopus |
| PMCID: | PMC4698793 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 80" - "Export Date: 4 June 2012" - "CODEN: NSMBC" - "Source: Scopus" |
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