Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein sex comb on midleg
Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein sex comb on midleg
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DOI：
10.1038/sj.embor.7401085
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发表时间：
2007-11-01
期刊：
影响因子：
7.7
通讯作者：
Mueller, Christoph W.
中科院分区：
文献类型：
--
作者：
Grimm, Clemens;de Ayala Alonso, Andres Gaytan;Mueller, Christoph W.
腿中部性梳（Scm）是果蝇中参与维持Hox和其他发育控制基因抑制的Polycomb蛋白质组的成员。Scm的两个恶性脑肿瘤（MBT）重复序列形成一个结构域，该结构域优先与作为游离氨基酸或肽的单甲基化赖氨酸残基结合，而未修饰或二甲基化或三甲基化赖氨酸残基以显著较低的亲和力结合。与MBT重复结构域结合的含单甲基赖氨酸的组蛋白尾肽的晶体结构表明，甲基赖氨酸侧链占据由三个保守的芳香族残基和一个天冬氨酸形成的第二MBT重复中的结合口袋。单甲基化侧链插入该口袋似乎是结合亲和力的主要贡献者。在果蝇中的功能分析表明，MBT结构域的Scm和它的甲基赖氨酸结合活性所需的Hox基因的镇压。
Sex comb on midleg ( Scm) is a member of the Polycomb group of proteins involved in the maintenance of repression of Hox and other developmental control genes in Drosophila. The two malignant brain tumour ( MBT) repeats of Scm form a domain that preferentially binds to monomethylated lysine residues either as a free amino acid or in the context of peptides, while unmodified or di- or trimethylated lysine residues are bound with significantly lower affinity. The crystal structure of a monomethyl- lysine-containing histone tail peptide bound to the MBT repeat domain shows that the methyl- lysine side chain occupies a binding pocket in the second MBT repeat formed by three conserved aromatic residues and one aspartate. Insertion of the monomethylated side chain into this pocket seems to be the main contributor to the binding affinity. Functional analyses in Drosophila show that the MBT domain of Scm and its methyl- lysine- binding activity are required for repression of Hox genes.