Article
- The EMBO Journal (2006) 25, 4245 - 4252
- doi:10.1038/sj.emboj.7601316
Published online: 31 August 2006
Subject Categories:
Structural basis for molecular recognition and presentation of histone H3 By WDR5
Anja Schuetz, Abdellah Allali-Hassani, Fernando Martín, Peter Loppnau, Masoud Vedadi, Alexey Bochkarev, Alexander N Plotnikov, Cheryl H Arrowsmith and Jinrong Min
- Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada
Correspondence to:
Jinrong Min, Structural Genomics Consortium, University of Toronto, 100 College St., Toronto, Ontario, Canada M5G 1L6. Tel.: +1 416 946 0957; Fax: +1 416 946 0588; E-mail: jr.min@utoronto.ca
Received 15 May 2006; Accepted 8 August 2006
Abstract
Histone methylation at specific lysine residues brings about various downstream events that are mediated by different effector proteins. The WD40 domain of WDR5 represents a new class of histone methyl-lysine recognition domains that is important for recruiting H3K4 methyltransferases to K4-dimethylated histone H3 tail as well as for global and gene-specific K4 trimethylation. Here we report the crystal structures of full-length WDR5, WDR5
23 and its complexes with unmodified, mono-, di- and trimethylated histone H3K4 peptides. The structures reveal that WDR5 is able to bind all of these histone H3 peptides, but only H3K4me2 peptide forms extra interactions with WDR5 by use of both water-mediated hydrogen bonding and the altered hydrophilicity of the modified lysine 4. We propose a mechanism for the involvement of WDR5 in binding and presenting histone H3K4 for further methylation as a component of MLL complexes.
Keywords:
- chromatin,
- methyl-lysine recognition,
- WDR5
