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 Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 28 Nov 2014 10:11 |
| Last Modified: | 02 Aug 2023 17:14 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/11132 |
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