Crystallographic studies of the ribosomal A-site molecular switches by using model RNA oligomers
Crystallographic studies of the ribosomal A-site molecular switches by using model RNA oligomers
复制标题
使用模型 RNA 寡聚物对核糖体 A 位分子开关进行晶体学研究
DOI：
10.1007/978-1-4939-2763-0_20
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Jiro Kondo
中科院分区：
文献类型：
--
作者：
近藤次郎;近藤次郎;近藤次郎;Jiro Kondo
位于核糖体氨酰-tRNA解码位点(A位)的RNA分子开关在蛋白质生物合成的解码过程中起着关键作用。该开关通过将单个同源tRNA的构象从“OFF”改变为“ON”状态，并识别密码子-反密码子微小螺旋的前两个碱基对，以检查这些碱基对是否属于典型的Watson-Crick类型，从而区分单个同源tRNA和近同源tRNA。氨基糖苷类抗生素专门针对细菌A位分子开关的“开”状态，扰乱解码过程的保真度，导致细胞死亡。如果它发生在服用氨基糖苷类药物的人类身上，可能会导致不良副作用。为了了解氨基糖苷类化合物解码的分子基础以及氨基糖苷类化合物的抗菌和毒副作用，有必要确定氨基糖苷类化合物存在和不存在时A位分子开关的三维结构。本章重点介绍了利用模型RNA低聚物研究A位开关的结晶学方法。该方法可用于任何DNA/RNA齐聚物的结晶学研究。
An RNA molecular switch in the aminoacyl-tRNA decoding site (A site) of the ribosome plays a key role in the decoding process of the protein biosynthesis. The switch discriminates a single cognate-tRNA from near-cognate tRNAs by changing its conformation from “off” to “on” states and recognizing the first two base pairs of codon–anticodon mini-helix to check whether these base pairs are of the canonical Watson–Crick type or not. Aminoglycoside antibiotics specifically target the “on” state of the bacterial A-site molecular switch and disturb the fidelity of the decoding process, resulting to cell death. If it occurs in human who was given aminoglycosides, it can lead to undesirable side effects. In order to understand the molecular bases of the decoding and the antibacterial and toxic side effects of aminoglycosides, it is necessary to determine the three-dimensional structures of the A-site molecular switches both in the presence and absence of aminoglycosides. This chapter focuses on methods in crystallographic studies of the A-site switches by using model RNA oligomers. The methods can be utilized in crystallographic studies of any DNA/RNA oligomers.