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Structure of translation factor elF4E bound to m7GDP and interaction with 4E-binding protein

Nature Structural Biologyvolume 4pages717724 (1997) | Download Citation



elF4E, the mRNA cap binding protein, is a master switch that controls eukaryotic translation. To be active, it must bind elF4G and form the elF4F complex, which also contains elF4A. Translation is downregulated by association of elF4E with 4E-BP, which occupies the elF4G binding site. Signalling events acting on 4E-BP cause it to dissociate from elF4E, and elF4E is then free to bind elF4G to form the active elF4F complex. We have solved the structure of the yeast elF4E/m7Gpp complex in a CHAPS micelle. We determined the position of the second nucleotide in a complex with m7GpppA, and identified the 4E-BP binding site. elF4E has a curved eight-stranded antiparallel β-sheet, decorated with three helices on the convex face and three smaller helices inserted in connecting loops. The m7G of the cap is intercalated into a stack of tryptophans in the concave face. The 4E-BP binding site is located in a region encompassing one edge of the β-sheet, the adjacent helix a2 and several regions of non-regular secondary structure. It is adjacent to, but does not overlap the cap-binding site.

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  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, USA

    • Hiroshi Matsuo
    • , Hanjun Li
    • , Abigail M. McGuire
    • , C. Mark Fletcher
    •  & Gerhard Wagner
  2. Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, H3G 1Y6, Canada

    • Anne-Claude Gingras
    •  & Nahum Sonenberg


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