Cat. No.

CBCRY09

Background

The WD40 repeat protein WDR5 specifically associates with the K4-methylated histone H3 in human cells. The structure of WDR5 in complex with a dimethylated H3-K4 peptide was deterimined. Unlike the chromodomain that recognizes the methylated H3-K4 through a hydrophobic cage, the specificity of WDR5 for methylated H3-K4 is conferred by the nonconventional hydrogen bonds between the two zeta-methyl groups of the dimethylated Lys4 and the carboxylate oxygen of Glu322 in WDR5. The three amino acids Ala-Arg-Thr preceding Lys4 form most of the specific contacts with WDR5, with Ala1 forming intermolecular hydrogen bonds and salt bridges, and the side chain of Arg2 inserting into the central channel of WDR5.

Molecular description

Protein Classification

Structural protein and DNA binding protein

Structure Weight

35306.44 Da

Polymer

1

Molecule

WD-repeat protein 5 

Chain Length

311 amino acids

Polymer

2

Molecule

Histone H3  

Chain Length

18 amino acids

Crystal Description

PDB ID

2G9A

MMDB ID

41532

Source

E.coli

Method

X-Ray Diffraction

Resolution

2.7 Å

Gene information

Gene Name

WDR5

Synonyms

BIG-3; BIG3; BMP2-induced 3-kb gene protein; SWD3, Set1c WD40 repeat protein, homolog; WD-repeat protein 5; WD repeat domain 5

UniProt ID

P61964

GeneID

11091

Chromosome  Location

9q34

Function

protein binding

Reference

Han Z, Guo L, Wang H, Shen Y, Deng XW, Chai J. Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol. Cell 2006, 22(1):137-44.