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

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Science  09 Mar 2001:
Vol. 291, Issue 5510, pp. 1959-1962
DOI: 10.1126/science.1058409

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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.

  • * These authors contributed equally to this work.

  • Present address: Department of Biochemistry, University of Texas, Health Science Center, Houston, TX 77030, USA.

  • To whom correspondence should be addressed. E-mail: doudna{at} and joachim{at}

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