The Zα domain from human ADAR1 binds to the Z-DNA conformer of many different sequences
The Zα domain from human ADAR1 binds to the Z-DNA conformer of many different sequences
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DOI：
10.1093/nar/26.15.3486
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发表时间：
1998-08-01
影响因子：
14.9
通讯作者：
Rich, A
中科院分区：
文献类型：
--
作者：
Herbert, A;Schade, M;Rich, A
Z-DNA是DNA的左手构象异构体，它通过RNA聚合酶在基因中移动时产生的负超螺旋来稳定。最近，我们已经证明编辑酶ADAR 1（双链RNA腺苷脱氨酶，1型）具有两个Z-DNA结合基序，Z α和Z β，其功能目前尚不清楚。在这里，我们表明，含有Z α基序的肽与Z-DNA以高亲和力结合为二聚体，结合位点不大于6 bp，Z α结构域可以翻转一系列序列，包括d（TA）（3），进入Z-DNA构象。还提出证据表明，Z α和Z β相互作用，形成一个功能性的DNA结合位点。原子力显微镜的研究表明，Z α与超螺旋质粒的结合与质粒的松弛有关。观察到明显的DNA扭结，并且似乎是由Z α的结合诱导的。这里报道的结果支持一种模型，其中Z-DNA结合基序将ADAR 1靶向活跃转录基因中的负超螺旋区域。在这种情况下，Z α的结合将取决于负超螺旋度的局部水平，而不是任何特定序列的存在。
Z-DNA, the left-handed conformer of DNA, is stabilized by the negative supercoiling generated during the movement of an RNA polymerase through a gene. Recently, we have shown that the editing enzyme ADAR1 (double-stranded RNA adenosine deaminase, type 1) has two Z-DNA binding motifs, Z alpha and Z beta, the function of which is currently unknown. Here we show that a peptide containing the Z alpha motif binds with high affinity to Z-DNA as a dimer, that the binding site is no larger than 6 bp and that the Z alpha domain can flip a range of sequences, including d(TA)(3), into the Z-DNA conformation. Evidence is also presented to show that Z alpha and Z beta interact to form a functional DNA binding site. Studies with atomic force microscopy reveal that binding of Z alpha to supercoiled plasmids is associated with relaxation of the plasmid. Pronounced kinking of DNA is observed, and appears to be induced by binding of Z alpha. The results reported here support a model where the Z-DNA binding motifs target ADAR1 to regions of negative supercoiling in actively transcribing genes. In this situation, binding by Z alpha would be dependent upon the local level of negative superhelicity rather than the presence of any particular sequence.