3EG6

Structure of WDR5 bound to MLL1 peptide

Summary for 3EG6

• Entry DOI: 10.2210/pdb3eg6/pdb
• Descriptor: WD repeat-containing protein 5, MLL-1 peptide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: wdr5, mll1, win motif, mll core complex, histone h3, lysine methylation, nucleus, phosphoprotein, wd repeat, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P61964; Nucleus . MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164
• Total number of polymer chains: 2
• Total formula weight: 35932.64

Authors

Patel, A.,Dharmarajan, V.,Cosgrove, M.S. (deposition date: 2008-09-10, release date: 2008-09-30, Last modification date: 2024-10-16)

Primary citation

Patel, A.,Dharmarajan, V.,Cosgrove, M.S.
Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide.
J.Biol.Chem., 283:32158-32161, 2008

PubMed Abstract: The mixed lineage leukemia protein-1 (MLL1) catalyzes histone H3 lysine 4 methylation and is regulated by interaction with WDR5 (WD-repeat protein-5), RbBP5 (retinoblastoma-binding protein-5), and the Ash2L (absent, small, homeotic discs-2-like) oncoprotein. In the accompanying investigation, we describe the identification of a conserved arginine containing motif, called the "Win" or WDR5 interaction motif, that is essential for the assembly and H3K4 dimethylation activity of the MLL1 core complex. Here we present a 1.7-A crystal structure of WDR5 bound to a peptide derived from the MLL1 Win motif. Our results show that Arg-3765 of MLL1 is bound in the same arginine binding pocket on WDR5 that was previously suggested to bind histone H3. Thermodynamic binding experiments show that the MLL1 Win peptide is preferentially recognized by WDR5. These results are consistent with a model in which WDR5 recognizes Arg-3765 of MLL1, which is essential for the assembly and enzymatic activity of the MLL1 core complex.

PubMed: 18829459
DOI: 10.1074/jbc.C800164200

Experimental method

X-RAY DIFFRACTION (1.72 Å)