A Database of Drosophila Genes & Genomes

FB2013_03, released May 7th, 2013
 

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Citation Kinch, L.N., Yarbrough, M.L., Orth, K., Grishin, N.V. (2009). Fido, a novel AMPylation domain common to fic, doc, and AvrB.  PLoS ONE 4(6): e5818. (Export to RIS)
FlyBase ID FBrf0208213
Publication Type Research paper
PubMed ID 19503829
PubMed Abstract The Vibrio parahaemolyticus type III secreted effector VopS contains a fic domain that covalently modifies Rho GTPase threonine with AMP to inhibit downstream signaling events in host cells. The VopS fic domain includes a conserved sequence motif (HPFx[D/E]GN[G/K]R) that contributes to AMPylation. Fic domains are found in a variety of species, including bacteria, a few archaea, and metazoan eukaryotes.We show that the AMPylation activity extends to a eukaryotic fic domain in Drosophila melanogaster CG9523, and use sequence and structure based computational methods to identify related domains in doc toxins and the type III effector AvrB. The conserved sequence motif that contributes to AMPylation unites fic with doc. Although AvrB lacks this motif, its structure reveals a similar topology to the fic and doc folds. AvrB binds to a peptide fragment of its host virulence target in a similar manner as fic binds peptide substrate. AvrB also orients a phosphate group from a bound ADP ligand near the peptide-binding site and in a similar position as a bound fic phosphate.The demonstrated eukaryotic fic domain AMPylation activity suggests that the VopS effector has exploited a novel host posttranslational modification. Fic domain-related structures give insight to the AMPylation active site and to the VopS fic domain interaction with its host GTPase target. These results suggest that fic, doc, and AvrB stem from a common ancestor that has evolved to AMPylate protein substrates.
DOI 10.1371/journal.pone.0005818
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Language of Publication English
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Publication Type Journal
Abbreviation PLoS ONE
Title PLoS ONE
Publication Year 2006-
ISBN/ISSN 1932-6203
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