Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5

被引：136

作者：

Han, ZF ^{[1
]}

Guo, L ^{[1
]}

Wang, HY ^{[1
]}

Shen, Y ^{[1
]}

Deng, XW ^{[1
]}

Chai, JJ ^{[1
]}

机构：

[1] Natl Inst Biol Sci, Beijing 102206, Peoples R China

来源：

MOLECULAR CELL | 2006年 / 22卷 / 01期

关键词：

D O I：

10.1016/j.molcel.2006.03.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The WD40 repeat protein WDRS specifically associates with the K4-methylated histone H3 in human cells. To investigate the structural basis for this specific recognition, we have determined the structure of WDR5 in complex with a dimethylated H3-K4 peptide at 1.9 angstrom resolution. 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. Both structural and biochemical studies presented here suggest another mode of recognition for the methylated histone tall.

引用

页码：137 / 144

页数：8

共 33 条

[1] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].