Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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5' Untranslated Regions / chemistry
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5' Untranslated Regions / metabolism*
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Animals
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Base Sequence
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Cryoelectron Microscopy
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Hepacivirus / genetics
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Hepacivirus / metabolism*
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Hepacivirus / ultrastructure
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Image Processing, Computer-Assisted
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Nucleic Acid Conformation
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RNA, Messenger / metabolism
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RNA, Ribosomal, 18S / chemistry
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RNA, Ribosomal, 18S / metabolism
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RNA, Viral / chemistry
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RNA, Viral / metabolism*
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Rabbits
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Ribosomes / chemistry*
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Ribosomes / metabolism*
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Ribosomes / ultrastructure
Substances
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5' Untranslated Regions
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Macromolecular Substances
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RNA, Messenger
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RNA, Ribosomal, 18S
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RNA, Viral