A complete methyl-lysine binding aromatic cage constructed by two domains of PHF2.
A complete methyl-lysine binding aromatic cage constructed by two domains of PHF2.
复制标题
DOI：
10.1016/j.jbc.2022.102862
复制
发表时间：
2023-02
影响因子：
4.8
通讯作者：
Cheng, Xiaodong
中科院分区：
文献类型：
--
作者：
Horton, John R.;Zhou, Jujun;Chen, Qin;Zhang, Xing;Bedford, Mark T.;Cheng, Xiaodong
PHF 2的N-末端一半含有植物同源结构域（PHD）和Jumonji结构域。PHD识别组蛋白H3三甲基化赖氨酸4和甲基化非组蛋白蛋白，包括牛痘相关激酶1（VRK 1）。Jumonji结构域在选择启动子处从组蛋白H3赖氨酸9（H3 K9 me 2）擦除抑制性二甲基化标记。H3（AR 2 TK 4）和VRK 1（PR 2 VK 4）的N-末端氨基酸序列在位置2处具有精氨酸并且在位置4处具有赖氨酸。在这里，我们表明PHF 2 N-末端半结合H3和VRK 1肽含有K4 me 3，解离常数（KD值）分别为160 nM和42 nM，这是4倍和21倍低（和更高的亲和力）比PHF 2的分离PHD结构域。X-射线晶体学显示，K4 me 3含有肽位于PHD和Jumonji界面内，带正电荷的R2残基接合PHD和Jumonji结构域的酸性残基，并且K4 me 3部分被来自两个结构域的芳香族残基包围。我们建议，微摩尔结合亲和力通常观察到的分离的甲基-赖氨酸阅读域可以通过在相同的多肽或其结合伙伴的额外的功能相互作用得到改善。
The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 and methylated nonhistone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (AR2TK4) and VRK1 (PR2VK4) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (KD values) of 160 nM and 42 nM, respectively, which are 4 × and 21 × lower (and higher affinities) than for the isolated PHD domain of PHF2. X-ray crystallography revealed that the K4me3-containing peptide is positioned within the PHD and Jumonji interface, with the positively charged R2 residue engaging acidic residues of the PHD and Jumonji domains and with the K4me3 moiety encircled by aromatic residues from both domains. We suggest that the micromolar binding affinities commonly observed for isolated methyl-lysine reader domains could be improved via additional functional interactions within the same polypeptide or its binding partners.
登录
查看更多内容
影响因子：
16.6
作者：
Bricambert J;Alves-Guerra MC;Esteves P;Prip-Buus C;Bertrand-Michel J;Guillou H;Chang CJ;Vander Wal MN;Canonne-Hergaux F;Mathurin P;Raverdy V;Pattou F;Girard J;Postic C;Dentin R
通讯作者：
Dentin R
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7.7
作者：
Grimm, Clemens;de Ayala Alonso, Andres Gaytan;Mueller, Christoph W.
通讯作者：
Mueller, Christoph W.
影响因子：
56.9
作者：
Huang, Y;Fang, J;Xu, RM
通讯作者：
Xu, RM
影响因子：
5.6
作者：
Gatchalian J;Ali M;Andrews FH;Zhang Y;Barrett AS;Kutateladze TG
通讯作者：
Kutateladze TG