4U0U

Wild type eukaryotic fic domain containing protein with ADP

Summary for 4U0U

• Entry DOI: 10.2210/pdb4u0u/pdb
• Related: 4UO4
• Descriptor: Adenosine monophosphate-protein transferase FICD, TETRAETHYLENE GLYCOL, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: tpr, fic, adp, adenylation, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane ; Single-pass membrane protein : Q9BVA6
• Total number of polymer chains: 2
• Total formula weight: 80582.24

Authors

Cole, A.R.,Bunney, T.D.,Katan, M. (deposition date: 2014-07-14, release date: 2014-12-10, Last modification date: 2024-05-08)

Primary citation

Bunney, T.D.,Cole, A.R.,Broncel, M.,Esposito, D.,Tate, E.W.,Katan, M.
Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions.
Structure, 22:1831-1843, 2014

PubMed 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.

PubMed: 25435325
DOI: 10.1016/j.str.2014.10.007

Experimental method

X-RAY DIFFRACTION (2.98 Å)