不同的结合模式决定了JMJD2A- Tudor结构域对甲基化组蛋白H3K4和H4K20的识别。
Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor.
作者信息
Lee Joseph, Thompson James R, Botuyan Maria Victoria, Mer Georges
机构信息
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
出版信息
Nat Struct Mol Biol. 2008 Jan;15(1):109-11. doi: 10.1038/nsmb1326. Epub 2007 Dec 16.
Abstract
The lysine demethylase JMJD2A has the unique property of binding trimethylated peptides from two different histone sequences (H3K4me3 and H4K20me3) through its tudor domains. Here we show using X-ray crystallography and calorimetry that H3K4me3 and H4K20me3, which are recognized with similar affinities by JMJD2A, adopt radically different binding modes, to the extent that we were able to design single point mutations in JMJD2A that inhibited the recognition of H3K4me3 but not H4K20me3 and vice versa.
摘要
赖氨酸去甲基化酶JMJD2A具有独特的特性，即通过其 Tudor 结构域与来自两种不同组蛋白序列（H3K4me3和H4K20me3）的三甲基化肽段结合。在此，我们利用X射线晶体学和量热法表明，JMJD2A以相似亲和力识别的H3K4me3和H4K20me3采用了截然不同的结合模式，以至于我们能够在JMJD2A中设计单点突变，抑制其对H3K4me3的识别但不影响对H4K20me3的识别，反之亦然。
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