Spahn C M, Kieft J S, Grassucci R A, Penczek P A, Zhou K, Doudna J A, Frank J
Howard Hughes Medical Institute, Health Research Inc. at the, Wadsworth Center, Empire State Plaza, Albany, New York 12201-0509, USA.
Science. 2001 Mar 9;291(5510):1959-62. doi: 10.1126/science.1058409.
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 A 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.
真核生物中蛋白质合成的起始需要将40S核糖体亚基招募到信使核糖核酸（mRNA）上。在大多数情况下，这依赖于对mRNA 5'端修饰核苷酸帽的识别。然而，另一条途径利用信使RNA或病毒RNA的5'非翻译区中一种名为内部核糖体进入位点（IRES）的结构化RNA元件。在此，我们展示了丙型肝炎病毒（HCV）IRES与40S核糖体亚基结合的冷冻电镜图谱，分辨率约为20埃。IRES结合在40S亚基中诱导了显著的构象变化，并关闭了mRNA结合裂隙，这提示了一种IRES介导的mRNA在核糖体解码中心定位的机制。
