Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein.
Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein.
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DOI：
10.1093/nar/gkp647
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发表时间：
2009-10
影响因子：
14.9
通讯作者：
Katahira M
中科院分区：
文献类型：
--
作者：
Mashima T;Matsugami A;Nishikawa F;Nishikawa S;Katahira M
获得了针对牛朊病毒蛋白（bPrP）的RNA适体，发现大多数获得的适体含有r（GGAGGAGGAGGA）（R12）序列。然后，揭示了R12以高亲和力结合bPrP及其β-同种型两者。在这里，我们介绍了R12的结构。这是第一份关于朊蛋白RNA适体结构的报告。R12形成分子内平行四链体。四链体含有G：G：G：G四联体和G（：A）：G：G（：A）：G六联体平面。两个四链体通过分子间六-六堆积形成二聚体。两个赖氨酸簇的bPrP已被确定为结合位点的R12。R12的独特排列的磷酸基团和赖氨酸簇之间的静电相互作用被认为是负责R12的亲和力bPrP。G：G：G：G四分体平面和色氨酸残基之间的堆积相互作用也可能有助于亲和力。一个R12二聚体分子应该同时结合一个bPrP分子的两个赖氨酸簇，导致甚至更高的亲和力。R12的原子坐标对于R12作为针对朊病毒疾病和阿尔茨海默病的治疗剂的开发将是有用的。
RNA aptamers against bovine prion protein (bPrP) were obtained, most of the obtained aptamers being found to contain the r(GGAGGAGGAGGA) (R12) sequence. Then, it was revealed that R12 binds to both bPrP and its β-isoform with high affinity. Here, we present the structure of R12. This is the first report on the structure of an RNA aptamer against prion protein. R12 forms an intramolecular parallel quadruplex. The quadruplex contains G:G:G:G tetrad and G(:A):G:G(:A):G hexad planes. Two quadruplexes form a dimer through intermolecular hexad–hexad stacking. Two lysine clusters of bPrP have been identified as binding sites for R12. The electrostatic interaction between the uniquely arranged phosphate groups of R12 and the lysine clusters is suggested to be responsible for the affinity of R12 to bPrP. The stacking interaction between the G:G:G:G tetrad planes and tryptophan residues may also contribute to the affinity. One R12 dimer molecule is supposed to simultaneously bind the two lysine clusters of one bPrP molecule, resulting in even higher affinity. The atomic coordinates of R12 would be useful for the development of R12 as a therapeutic agent against prion diseases and Alzheimer's disease.
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影响因子：
14.9
作者：
Matsugami, Akimasa;Ohyama, Takako;Katahira, Masato
通讯作者：
Katahira, Masato
影响因子：
5.6
作者：
Liu, H;Matsugami, A;Uesugi, S
通讯作者：
Uesugi, S
影响因子：
64.8
作者：
Riek, R;Hornemann, S;Wuthrich, K
通讯作者：
Wuthrich, K
影响因子：
5.6
作者：
Matsugami, A;Ouhashi, K;Katahira, M
通讯作者：
Katahira, M
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH