Fido, a novel ampylation domain common to fic, doc, and AvrB

Lisa N. Kinch, Melanie L. Yarbrough, Kim Orth, Nick V. Grishin

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.

Original languageEnglish (US)
Article numbere5818
JournalPLoS One
Volume4
Issue number6
DOIs
StatePublished - Jun 5 2009

Fingerprint

Conserved Sequence
conserved sequences
Phosphates
guanosinetriphosphatase
peptides
Vibrio parahaemolyticus
rho GTP-Binding Proteins
Peptides
Peptide Fragments
GTP Phosphohydrolases
Archaea
Substrates
Threonine
Adenosine Monophosphate
Post Translational Protein Processing
Computational methods
Eukaryota
Drosophila melanogaster
phosphates
Adenosine Diphosphate

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fido, a novel ampylation domain common to fic, doc, and AvrB. / Kinch, Lisa N.; Yarbrough, Melanie L.; Orth, Kim; Grishin, Nick V.

In: PLoS One, Vol. 4, No. 6, e5818, 05.06.2009.

Research output: Contribution to journalArticle

Kinch, Lisa N. ; Yarbrough, Melanie L. ; Orth, Kim ; Grishin, Nick V. / Fido, a novel ampylation domain common to fic, doc, and AvrB. In: PLoS One. 2009 ; Vol. 4, No. 6.
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