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Science 9 March 2001:
Vol. 291. no. 5510, pp. 1959 - 1962
DOI: 10.1126/science.1058409
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Reports

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

Christian M. T. Spahn,12* Jeffrey S. Kieft,3* Robert A. Grassucci,12 Pawel A. Penczek,2dagger Kaihong Zhou,3 Jennifer A. Doudna,3ddagger Joachim Frank124dagger

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.

1 Howard Hughes Medical Institute, Health Research Inc. at the
2 Wadsworth Center, Empire State Plaza, Albany, New York 12201-0509, USA.
3 Department of Molecular Biophysics and Biochemistry and Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8114, USA.
4 Department of Biomedical Sciences, State University of New York at Albany, Albany, NY 12222, USA.
*   These authors contributed equally to this work.

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

ddagger    To whom correspondence should be addressed. E-mail: doudna{at}csb.yale.edu and joachim{at}wadsworth.org

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