Abstract
An 11.7-A-resolution cryo-EM map of the yeast 80S.eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges. Sordarin positions domain III of eEF2 so that it can interact with the sarcin-ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation explains the inhibitory action of sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state. A ratchet-like subunit rearrangement (RSR) occurs in the 80S.eEF2.sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes. A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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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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Antifungal Agents / pharmacology
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Cryoelectron Microscopy
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Crystallography, X-Ray
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Indenes
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Models, Molecular
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Movement
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Nucleic Acid Conformation
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Peptide Elongation Factor 2 / chemistry*
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Peptide Elongation Factor 2 / metabolism*
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Peptide Elongation Factor 2 / ultrastructure
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Protein Binding
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Protein Subunits / genetics
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Protein Subunits / metabolism
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RNA Transport
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RNA, Transfer / chemistry
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RNA, Transfer / genetics
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RNA, Transfer / metabolism*
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Ribosomes / chemistry*
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Ribosomes / metabolism*
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Ribosomes / ultrastructure
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Saccharomyces cerevisiae / chemistry
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae / ultrastructure
Substances
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Antifungal Agents
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Indenes
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Peptide Elongation Factor 2
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Protein Subunits
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sordarin
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RNA, Transfer