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

Initiation of protein synthesis in eukaryotes requires recruitment of the 4 0S ribosomal subunit to the messenger RNA(mRNA). In most cases, this depend s on recognition of a modified nucleotide cap on the 5' end of the mRNA. Ho wever, an alternate pathway uses a structured RNA element in the 5' untrans lated region of the messenger or viral RNA called an internal ribosomal ent ry site (IRES). Here, we present a cryo-electron microscopy map of the hepa titis C virus (HCV) IRES bound to the 40S ribosomal subunit at about 20 Ang strom resolution. IRES binding induces a pronounced conformational change i n the 40S subunit and closes the mRNA binding cleft, suggesting a mechanism for IRES-mediated positioning of mRNA in the ribosomal decoding center.