The HMGB1 C-Terminal Tail Regulates DNA Bending.
The HMGB1 C-Terminal Tail Regulates DNA Bending.
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DOI：
10.1016/j.jmb.2016.08.018
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发表时间：
2016-10-09
影响因子：
5.6
通讯作者：
Kugel JF
中科院分区：
文献类型：
--
作者：
Blair RH;Horn AE;Pazhani Y;Grado L;Goodrich JA;Kugel JF
HMGB 1（高迁移率族蛋白1）是一种结构蛋白，其促进参与转录、重组、DNA修复和染色质重塑的蛋白质-DNA组装体的形成。HMGB 1非序列特异性弯曲DNA的能力对其功能很重要。HMGB 1含有两个结合和弯曲DNA的HMG盒（A盒和B盒）和C末端酸性尾。我们研究了这些结构域如何有助于DNA弯曲HMGB 1使用单分子FRET，这使我们能够解决异质群体的弯曲和未弯曲的DNA。我们发现，全长HMGB 1弯曲DNA比单独的A和B盒。去除C-末端尾导致蛋白质比全长蛋白质更大程度地弯曲DNA。这些数据表明，A盒和B盒在没有C-末端尾的情况下同时结合DNA，但是尾通过全长蛋白质中的HMG盒之一调节DNA结合和弯曲。事实上，由B盒和C-末端尾部组成的构建体仅在较高蛋白质浓度下弯曲DNA。此外，在全长蛋白质的情况下，突变A盒使得其不能弯曲DNA导致蛋白质与单个HMG盒类似地弯曲DNA，并且仅在更高的蛋白质浓度下。我们提出了一个模型，其中HMGB 1的C-末端尾巴作为一个分子内阻尼器，调制的B盒与DNA的相互作用。
HMGB1 (high mobility group box protein 1) is an architectural protein that facilitates formation of protein-DNA assemblies involved in transcription, recombination, DNA repair, and chromatin remodeling. Important to its function is the ability of HMGB1 to bend DNA non-sequence specifically. HMGB1 contains two HMG boxes that bind and bend DNA (the A box and the B box) and a C-terminal acidic tail. We investigated how these domains contribute to DNA bending by HMGB1 using single molecule FRET, which enabled us to resolve heterogeneous populations of bent and unbent DNA. We found that full length HMGB1 bent DNA more than the individual A and B boxes. Removing the C-terminal tail resulted in a protein that bent DNA to a greater extent than the full length protein. These data suggest that the A and B boxes simultaneously bind DNA in the absence of the C-terminal tail, but the tail modulates DNA binding and bending by one of the HMG boxes in the full length protein. Indeed, a construct composed of the B box and the C-terminal tail only bent DNA at higher protein concentrations. Moreover, in the context of the full length protein, mutating the A box such that it could not bend DNA resulted in a protein that bent DNA similarly to a single HMG box and only at higher protein concentrations. We propose a model in which the HMGB1 C-terminal tail serves as an intramolecular damper that modulates the interaction of the B box with DNA.
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