Bunney, TD;
Cole, AR;
Broncel, M;
Esposito, D;
Tate, EW;
Katan, M;
(2014)
Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions.
Structure
, 22
(12)
1831 - 1843.
10.1016/j.str.2014.10.007.
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1-s2.0-S0969212614003347-main.pdf Download (3MB) |
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 auto AMPylation 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.
Type: | Article |
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Title: | Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions. |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.str.2014.10.007 |
Publisher version: | http://dx.doi.org/10.1016/j.str.2014.10.007 |
Language: | English |
Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
URI: | https://discovery.ucl.ac.uk/id/eprint/1458476 |
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