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Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

DOI: 10.1016/j.str.2014.10.007 DOI Help
PMID: 25435325 PMID Help

Authors: Tom d. Bunney (Division of Biosciences, Institute of Structural and Molecular Biology, University College London) , Ambrose Cole (Institute of Structural and Molecular Biology, Birkbeck College) , Malgorzata Broncel (Department of Chemistry, Imperial College London) , Diego Esposito (Division of Molecular Structure, MRC-National Institute for Medical Research) , Edward W. Tate (Department of Chemistry, Imperial College London) , Matilda Katan (Division of Biosciences, Institute of Structural and Molecular Biology, University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 22 (12) , PAGES 1831 - 1843

State: Published (Approved)
Published: December 2014

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: ESRF, SOLEIL

Added On: 24/02/2015 10:24

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1-s2.0-S0969212614003347-main.pdf

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