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  • The EMBO Journal (2007) 26, 3936 - 3944
  • doi:10.1038/sj.emboj.7601817

Published online: 9 August 2007

Structural insights into the transcriptional and translational roles of Ebp1

Tom P Monie1, Andrew J Perrin1, James R Birtley1, Trevor R Sweeney1, Ioannis Karakasiliotis2, Yasmin Chaudhry2, Lisa O Roberts3, Stephen Matthews4, Ian G Goodfellow2 and Stephen Curry1

  1. Division of Cell and Molecular Biology, Imperial College, South Kensington Campus, London, UK
  2. Department of Virology, Faculty of Medicine, Imperial College London, London, UK
  3. School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
  4. Division of Biomolecular Science, Imperial College, London, UK

Correspondence to:

Stephen Curry, Division of Cell and Molecular Biology, Imperial College, South Kensington Campus, London SW7 2AZ, UK. Tel.: +44 20 7594 7632; Fax: +44 20 7589 0191; E-mail: s.curry@imperial.ac.uk

Received 2 February 2007; Accepted 11 July 2007

The ErbB3-binding protein 1 (Ebp1) is an important regulator of transcription, affecting eukaryotic cell growth, proliferation, differentiation and survival. Ebp1 can also affect translation and cooperates with the polypyrimidine tract-binding protein (PTB) to stimulate the activity of the internal ribosome entry site (IRES) of foot-and-mouth disease virus (FMDV). We report here the crystal structure of murine Ebp1 (p48 isoform), providing the first glimpse of the architecture of this versatile regulator. The structure reveals a core domain that is homologous to methionine aminopeptidases, coupled to a C-terminal extension that contains important motifs for binding proteins and RNA. It sheds new light on the conformational differences between the p42 and p48 isoforms of Ebp1, the disposition of the key protein-interacting motif (354LKALL358) and the RNA-binding activity of Ebp1. We show that the primary RNA-binding site is formed by a Lys-rich motif in the C terminus and mediates the interaction with the FMDV IRES. We also demonstrate a specific functional requirement for Ebp1 in FMDV IRES-directed translation that is independent of a direct interaction with PTB.

  • Keywords:

    • crystal structure,
    • Ebp1/ITAF45/PA2G4,
    • IRES,
    • RNA-binding,
    • translation initiation