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Publication Abstract from PubMed

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.

Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions.,Bunney TD, Cole AR, Broncel M, Esposito D, Tate EW, Katan M Structure. 2014 Nov 25. pii: S0969-2126(14)00334-7. doi:, 10.1016/j.str.2014.10.007. PMID:25435325^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.