Hepatitis C Virus IRES RNA-Induced Changes in the Conformation of the 40S Ribosomal Subunit

CMT Spahn, JS Kieft, RA Grassucci, PA Penczek… - Science, 2001 - science.org
Science, 2001science.org
Initiation of protein synthesis in eukaryotes requires recruitment of the 40 S 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 40 S ribosomal subunit at about 20 Å …
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 Å 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.
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