Full activation of RNaseL in animal cells requires binding of 2-5A within ankyrin repeats 6 to 9 of this interferon-inducible enzyme
Full activation of RNaseL in animal cells requires binding of 2-5A within ankyrin repeats 6 to 9 of this interferon-inducible enzyme
复制标题
DOI：
10.1089/107999099314252
复制
发表时间：
1999-02-01
影响因子：
2.3
通讯作者：
Esteban, M
中科院分区：
文献类型：
--
作者：
Díaz-Guerra, M;Rivas, C;Esteban, M
为了确定干扰素（IFN）诱导的2-5A合成酶依赖性RNaseL激活的重要蛋白结构域，我们产生了能够在培养细胞中表达该蛋白截断形式的痘苗病毒（VV）重组体，并将其与产生野生型酶的重组体的生物活性进行了比较，并在2-5A合成酶共表达和不共表达的情况下进行了比较。我们的研究结果表明，RNaseL的完全激活需要结合氨基酸位置212-339的2-5A寡核苷酸，对应于锚蛋白重复序列6至9。RNaseL的蛋白激酶和核糖核酸酶结构域，氨基酸340-741，对于一个对过量2-5A无反应的组成活性酶来说是足够的。这些结果在体内证明了锚蛋白结构域在RNaseL的生物学功能中的重要性，我们认为锚蛋白重复序列是RNaseL活性的关键调节因子。
To define protein domains important for activation of the interferon (IFN)-induced enzyme 2-5A-dependent RNaseL, we have generated vaccinia virus (VV) recombinants able to express in cultured cells truncated forms of this protein and compared their biologic activities with those producing the wild-type enzyme, with and without coexpression of 2-5A synthetase. Our results show that full activation of RNaseL requires binding of 2-5A oligonucleotides within amino acid positions 212-339, corresponding to ankyrin repeats 6 to 9. The protein kinase and ribonuclease domains of RNaseL, amino acids 340-741, are sufficient for a constitutively active enzyme that is unresponsive to excess 2-5A, These results demonstrate in vivo the importance of the ankyrin domains in the biologic function of RNaseL, We suggest that ankyrin repeats act as key modulators of RNaseL activity.