Document Detail

WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket.
MedLine Citation:
PMID:  18840606     Owner:  NLM     Status:  MEDLINE    
WDR5 is a component of the mixed lineage leukemia (MLL) complex, which methylates lysine 4 of histone H3, and was identified as a methylated Lys-4 histone H3-binding protein. Here, we present a crystal structure of WDR5 bound to an MLL peptide. Surprisingly, we find that WDR5 utilizes the same pocket shown to bind histone H3 for this MLL interaction. Furthermore, the WDR5-MLL interaction is disrupted preferentially by mono- and di-methylated Lys-4 histone H3 over unmodified and tri-methylated Lys-4 histone H3. These data implicate a delicate interplay between the effector, WDR5, the catalytic subunit, MLL, and the substrate, histone H3, of the MLL complex. We suggest that the activity of the MLL complex might be regulated through this interplay.
Ji-Joon Song; Robert E Kingston
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-08     Completed Date:  2009-02-19     Revised Date:  2013-02-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  35258-64     Citation Subset:  IM    
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
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MeSH Terms
Amino Acid Motifs
Amino Acid Sequence
Catalytic Domain
Crystallography, X-Ray
Histone-Lysine N-Methyltransferase / metabolism*
Histones / metabolism*
Molecular Sequence Data
Myeloid-Lymphoid Leukemia Protein / metabolism*
Protein Binding
Protein Conformation
Sequence Homology, Amino Acid
Surface Plasmon Resonance
Grant Support
Reg. No./Substance:
0/Histones; 0/MLL protein, human; 0/WDR5 protein, human; 149025-06-9/Myeloid-Lymphoid Leukemia Protein; EC N-Methyltransferase

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