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    Crystal structure of the human, FIC-Domain containing protein HYPE and implications for its functions

    Bunney, T.D. and Cole, Ambrose R. and Broncel, M. and Esposito, D. and Tate, E.W. and Katan, M. (2014) Crystal structure of the human, FIC-Domain containing protein HYPE and implications for its functions. Structure 22 (12), pp. 1831-1843. ISSN 0969-2126.

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    Abstract

    Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 28 Nov 2014 10:11
    Last Modified: 03 Dec 2014 10:06
    URI: http://eprints.bbk.ac.uk/id/eprint/11132

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