Hepatitis C virus IRES RNA-induced changes in the conformation of the 40S ribosomal subunit

Hepatitis C virus IRES RNA-induced changes in the conformation of the 40S ribosomal subunit
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DOI:
10.1126/science.1058409
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发表时间:
2001-03-09
期刊:
影响因子:
56.9
通讯作者:
Frank, J
Frank, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Spahn, CMT;Kieft, JS;Frank, J

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真核生物蛋白质合成的启动需要将40S核糖体亚基募集到信使RNA(MRNA)中。在大多数情况下,这取决于对信使核糖核酸5‘端修饰核苷酸帽的识别。然而,另一种途径使用信使或病毒RNA 5‘非翻译区的结构性RNA元件,称为内部核糖体进入位点(IRES)。在这里,我们提出了一个冷冻电子显微镜图谱,丙型肝炎病毒(丙型肝炎病毒)IRES结合的40S核糖体亚基约20埃分辨率。IRES结合诱导了40S亚基的显著构象变化,并关闭了mRNA结合裂隙,提示了IRES介导的mRNA在核糖体解码中心的定位机制。
Initiation of protein synthesis in eukaryotes requires recruitment of the 40S ribosomal subunit to the messenger RNA(mRNA). In most cases, this depends on recognition of a modified nucleotide cap on the 5' end of the mRNA. However, an alternate pathway uses a structured RNA element in the 5' untranslated region of the messenger or viral RNA called an internal ribosomal entry site (IRES). Here, we present a cryo-electron microscopy map of the hepatitis C virus (HCV) IRES bound to the 40S ribosomal subunit at about 20 Angstrom resolution. IRES binding induces a pronounced conformational change in the 40S subunit and closes the mRNA binding cleft, suggesting a mechanism for IRES-mediated positioning of mRNA in the ribosomal decoding center.