Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation.
Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation.
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Tau 蛋白与双链的小凹槽结合，可防止 DNA 因过氧化而受损。
DOI：
10.1371/journal.pone.0002600
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发表时间：
2008-07-02
期刊：
影响因子：
3.7
通讯作者：
He RQ
中科院分区：
文献类型：
--
作者：
Wei Y;Qu MH;Wang XS;Chen L;Wang DL;Liu Y;Hua Q;He RQ
Tau蛋白是一种重要的微管相关蛋白，它与DNA结合，并定位于神经元和一些非神经元细胞的细胞核中。在这里，使用电泳迁移率变动分析（EMSA）在不同链长的DNA的存在下，我们观察到，tau蛋白有利于结合到一个13 bp或更长的多核苷酸。原子力显微镜的结果也表明，tau蛋白更喜欢13 bp的多核苷酸，而不是12 bp或更短的多核苷酸。在竞争性测定中，小沟结合剂偏端霉素A能够从DNA双螺旋取代结合的tau，表明tau蛋白结合小沟。Tau蛋白能够在结合到小沟的DNase I存在下保护双链免于消化。另一方面，在EMSA中，作为负竞争剂的大沟结合剂甲基绿色对tau-DNA复合物的阻滞作用几乎没有表现出。这进一步表明DNA小沟作为tau蛋白的结合位点。EMSA与截短的tau蛋白表明，富含脯氨酸的结构域（PRD）和微管结合结构域（MTBD）有助于与DNA的相互作用，也就是说，PRD和MTBD结合到DNA的小沟和弯曲的双链，如通过电子显微镜观察。为了研究tau蛋白是否能够防止DNA受到羟基自由基的损伤，测量了phen-Cu/H2 O2/抗坏血酸盐的化学发光。当tau蛋白存在时，发光的发射强度显著降低，表明在羟基自由基存在下DNA免受损伤的显著保护。
Tau, an important microtubule associated protein, has been found to bind to DNA, and to be localized in the nuclei of both neurons and some non-neuronal cells. Here, using electrophoretic mobility shifting assay (EMSA) in the presence of DNA with different chain-lengths, we observed that tau protein favored binding to a 13 bp or a longer polynucleotide. The results from atomic force microscopy also showed that tau protein preferred a 13 bp polynucleotide to a 12 bp or shorter polynucleotide. In a competitive assay, a minor groove binder distamycin A was able to replace the bound tau from the DNA double helix, indicating that tau protein binds to the minor groove. Tau protein was able to protect the double-strand from digestion in the presence of DNase I that was bound to the minor groove. On the other hand, a major groove binder methyl green as a negative competitor exhibited little effect on the retardation of tau-DNA complex in EMSA. This further indicates the DNA minor groove as the binding site for tau protein. EMSA with truncated tau proteins showed that both the proline-rich domain (PRD) and the microtubule-binding domain (MTBD) contributed to the interaction with DNA; that is to say, both PRD and MTBD bound to the minor groove of DNA and bent the double-strand, as observed by electron microscopy. To investigate whether tau protein is able to prevent DNA from the impairment by hydroxyl free radical, the chemiluminescence emitted by the phen-Cu/H2O2/ascorbate was measured. The emission intensity of the luminescence was markedly decreased when tau protein was present, suggesting a significant protection of DNA from the damage in the presence of hydroxyl free radical.
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DOI：
10.1073/pnas.85.11.4051
发表时间：
1988-06-01
影响因子：
11.1
作者：
GOEDERT, M;WISCHIK, CM;KLUG, A
通讯作者：
KLUG, A
影响因子：
11.4
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
DOI：
10.1016/s1570-9639(02)00538-1
发表时间：
2003-02-21
影响因子：
3.2
作者：
Hua, Q;He, RQ
通讯作者：
He, RQ
影响因子：
16.2
作者：
LEE, G;NEVE, RL;KOSIK, KS
通讯作者：
KOSIK, KS