Folding transitions during assembly of the eukaryotic mRNA cap-binding complex

John Mccarthy, Tobias Von Der Haar, Yuko Oku, Marina Ptushkina, Nathan Moerke, Gerhard Wagner, John D. Gross, John E G McCarthy

    Research output: Contribution to journalArticlepeer-review


    The cap-binding protein eIF4E is the first in a chain of translation initiation factors that recruit 40 S ribosomal subunits to the 5′ end of eukaryotic mRNA. During cap-dependent translation, this protein binds to the 5′-terminal m7Gppp cap of the mRNA, as well as to the adaptor protein eIF4G. The latter then interacts with small ribosomal subunit-bound proteins, thereby promoting the mRNA recruitment process. Here, we show apo-eIF4E to be a protein that contains extensive unstructured regions, which are induced to fold upon recognition of the cap structure. Binding of eIF4G to apo-eIF4E likewise induces folding of the protein into a state that is similar to, but not identical with, that of cap-bound eIF4E. At the same time, binding of each of the binding partners of eIF4E modulates the kinetics with which it interacts with the other partner. We present structural, kinetic and mutagenesis data that allow us to deduce some of the detailed folding transitions that take place during the eIF4E interactions. © 2005 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)982-992
    Number of pages10
    JournalJournal of molecular biology
    Issue number4
    Publication statusPublished - 3 Mar 2006


    • Eukaryotic initiation factor
    • NMR
    • Protein folding
    • Surface plasmon resonance
    • Translation initiation


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