Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
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MBT 重复蛋白 L3MBTL2 对组蛋白的甲基化状态特异性识别
DOI：
10.1093/nar/gkp086
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发表时间：
2009-04
影响因子：
14.9
通讯作者：
Min J
中科院分区：
文献类型：
--
作者：
Guo Y;Nady N;Qi C;Allali-Hassani A;Zhu H;Pan P;Adams-Cioaba MA;Amaya MF;Dong A;Vedadi M;Schapira M;Read RJ;Arrowsmith CH;Min J
MBT重复序列最近被鉴定为能够识别甲基赖氨酸组蛋白的关键结构域。功能性研究表明，含MBT结构域的蛋白质在发育控制基因（如Hox基因）的转录抑制中发挥作用。在这项研究中，L3 MBTL 2，人类同源果蝇Sfmbt的关键Hox基因沉默，被证明优先识别低甲基化状态的几个组蛋白衍生肽通过其第四MBT重复。高分辨率晶体学分析的四个MBT重复的这种蛋白质揭示了其独特的不对称菱形结构，以及结合机制，这排除了相互作用的前三个MBT重复与甲基化的肽。L3 MBTL 2-H4 K20 me 1复合物的结构解析以及与其他MBT-组蛋白肽复合物的比较也表明，甲基赖氨酸结合口袋周围没有明显的表面轮廓可能是该蛋白质家族成员缺乏序列特异性的基础。
The MBT repeat has been recently identified as a key domain capable of methyl–lysine histone recognition. Functional work has pointed to a role for MBT domain-containing proteins in transcriptional repression of developmental control genes such as Hox genes. In this study, L3MBTL2, a human homolog of Drosophila Sfmbt critical for Hox gene silencing, is demonstrated to preferentially recognize lower methylation states of several histone-derived peptides through its fourth MBT repeat. High-resolution crystallographic analysis of the four MBT repeats of this protein reveals its unique asymmetric rhomboid architecture, as well as binding mechanism, which preclude the interaction of the first three MBT repeats with methylated peptides. Structural elucidation of an L3MBTL2–H4K20me1 complex and comparison with other MBT-histone peptide complexes also suggests that an absence of distinct surface contours surrounding the methyl–lysine-binding pocket may underlie the lack of sequence specificity observed for members of this protein family.
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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：
10.5
作者：
Min, JR;Zhang, Y;Xu, RM
通讯作者：
Xu, RM
影响因子：
56.9
作者：
Huang, Y;Fang, J;Xu, RM
通讯作者：
Xu, RM
影响因子：
16
作者：
Joshi, AA;Struhl, K
通讯作者：
Struhl, K