Molecular recognition of histone H3 by the WD40 protein WDR5
Molecular recognition of histone H3 by the WD40 protein WDR5
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DOI：
10.1038/nsmb1116
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发表时间：
2006-08-01
影响因子：
16.8
通讯作者：
Trievel, Raymond C.
中科院分区：
文献类型：
--
作者：
Couture, Jean-Francois;Collazo, Evys;Trievel, Raymond C.
WD 40-重复蛋白WDR 5是三胸（TRX）组蛋白甲基转移酶复合物的保守亚基。据报道，WDR 5选择性结合组蛋白H3中的二甲基化Lys 4（K4 me 2），以促进TRX对K4的三甲基化。为了阐明这种结合特异性的基础，我们已经确定了WDR 5的晶体结构结合到组蛋白H3肽轴承K4 me 2。该结构揭示了组蛋白H3的N末端作为3（10）-螺旋结合在由WD 40重复形成的中央凹陷中。组蛋白H3中的R2结合在蛋白质核心的酸性通道中，而K4 me 2暴露于溶剂中，不与WDR 5直接相互作用。功能研究证实，WDR 5识别组蛋白H3中的A1、R2和T3，但对K4的未修饰和单甲基化、二甲基化和三甲基化形式具有几乎相同的亲和力，表明它不能区分该残基的不同甲基化程度。
The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) histone methyltransferase complexes. WDR5 has been reported to selectively bind dimethylated Lys4 (K4me2) in histone H3 to promote K4 trimethylation by TRX. To elucidate the basis of this binding specificity, we have determined the crystal structure of WDR5 bound to a histone H3 peptide bearing K4me2. The structure reveals that the N terminus of histone H3 binds as a 3(10)-helix in the central depression formed by the WD40 repeats. R2 in histone H3 is bound in the acidic channel in the protein's core, whereas K4me2 is solvent exposed and does not engage in direct interactions with WDR5. Functional studies confirm that WDR5 recognizes A1, R2 and T3 in histone H3 but has virtually identical affinities for the unmodified and mono-, di- and trimethylated forms of K4, demonstrating that it does not discriminate among different degrees of methylation of this residue.