Transcriptional repressor domain of MBD1 is intrinsically disordered and interacts with its binding partners in a selective manner.
Transcriptional repressor domain of MBD1 is intrinsically disordered and interacts with its binding partners in a selective manner.
复制标题
DOI：
10.1038/srep04896
复制
发表时间：
2014-05-09
影响因子：
4.6
通讯作者：
Swaminathan K
中科院分区：
文献类型：
--
作者：
Hameed UF;Lim J;Zhang Q;Wasik MA;Yang D;Swaminathan K
DNA CpG位点甲基化是表观遗传学基因沉默的主要机制，在细胞分裂、发育和肿瘤发生中起重要作用。MBD 1的64个残基的C末端转录抑制结构域（TRD）是其调节因子之一，其募集几种抑制蛋白，如MCAF 1、HDAC 3和MPG，这些蛋白对于基因沉默是必需的。使用NMR光谱，我们已经表征了MBD 1的C-末端（MBD 1-c，残基D507至Q605）的溶液结构，其中包括TRD（A529至P592）。令人惊讶的是，MBD 1-c本质上是无序的。尽管它缺乏三级折叠，MBD 1-c仍然可以以选择性的方式与不同的伴侣蛋白结合。MPG和MCAF 1 Δ8显示与MBD 1-c的N-末端和C-末端残基结合，但HDAC 3优选与C-末端区域结合。这项研究揭示了MBD 1-c如何区分不同的结合伴侣，从而扩大了我们对MBD 1基因调控机制的理解。
Methylation of DNA CpG sites is a major mechanism of epigenetic gene silencing and plays important roles in cell division, development and carcinogenesis. One of its regulators is the 64-residue C-terminal Transcriptional Repressor Domain (the TRD) of MBD1, which recruits several repressor proteins such as MCAF1, HDAC3 and MPG that are essential for the gene silencing. Using NMR spectroscopy, we have characterized the solution structure of the C-terminus of MBD1 (MBD1-c, residues D507 to Q605), which included the TRD (A529 to P592). Surprisingly, the MBD1-c is intrinsically disordered. Despite its lack of a tertiary folding, MBD1-c could still bind to different partner proteins in a selective manner. MPG and MCAF1Δ8 showed binding to both the N-terminal and C-terminal residues of MBD1-c but HDAC3 preferably bound to the C-terminal region. This study reveals how MBD1-c discriminates different binding partners, and thus, expands our understanding of the mechanisms of gene regulation by MBD1.
登录
查看更多内容
影响因子：
23.9
作者：
Liu C;Teng ZQ;Santistevan NJ;Szulwach KE;Guo W;Jin P;Zhao X
通讯作者：
Zhao X
影响因子：
16.8
作者：
Baker, Jennifer M. R.;Hudson, Rhea P.;Forman-Kay, Julie D.
通讯作者：
Forman-Kay, Julie D.
影响因子：
11.4
作者：
Lyst, Matthew J.;Nan, Xinsheng;Stancheva, Irina
通讯作者：
Stancheva, Irina
影响因子：
30.8
作者：
Jones, PL;Veenstra, GJC;Wolffe, AP
通讯作者：
Wolffe, AP
影响因子：
5.3
作者：
Fujita, N;Shimotake, N;Nakao, M
通讯作者：
Nakao, M