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PMID: 16946699 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural basis for molecular recognition and presentation of histone H3 by WDR5.

The EMBO journal ·Vol. 25 ·No. 18 ·2006-09-20 ·Pages 4245-52

Schuetz A, Allali-Hassani A, Martín F, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Arrowsmith CH, Min J

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, WDR5Delta23 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.

MeSH Terms
Amino Acid Sequence Crystallography, X-Ray Heterotrimeric GTP-Binding Proteins/chemistry,genetics,metabolism Histone-Lysine N-Methyltransferase Histones/chemistry,metabolism Humans Hydrogen Bonding In Vitro Techniques Intracellular Signaling Peptides and Proteins Lysine/chemistry Methylation Models, Molecular Molecular Sequence Data Multiprotein Complexes Protein Binding Protein Structure, Tertiary Recombinant Proteins/chemistry,genetics,metabolism Sequence Homology, Amino Acid Thermodynamics
Chemicals
Histones Intracellular Signaling Peptides and Proteins Multiprotein Complexes Recombinant Proteins WDR5 protein, human Histone-Lysine N-Methyltransferase Heterotrimeric GTP-Binding Proteins Lysine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Schuetz Anja
Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
Allali-Hassani Abdellah
Martín Fernando
Loppnau Peter
Vedadi Masoud
Bochkarev Alexey
Plotnikov Alexander N
Arrowsmith Cheryl H
Min Jinrong
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601316
Published
2006-09-20
Epub
2006-00-31
Pages
4245-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1570438
Subset
IM
Grants
Wellcome Trust · United Kingdom
Databases
PDB
2GNQ, 2H9L, 2H9M, 2H9N, 2H9O, 2H9P
External Links
PubMed source DOI: 10.1038/sj.emboj.7601316 PMC Full Text View journal details
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