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Science. 2001 Mar 9;291(5510):1959-62.

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

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Howard Hughes Medical Institute, Health Research Inc. at the, Wadsworth Center, Empire State Plaza, Albany, New York 12201-0509, USA.


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.

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