title: AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling.
abstract: The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of the actin cytoskeleton by inhibiting Rho guanosine triphosphatases (GTPases). We found that VopS could act to covalently modify a conserved threonine residue on Rho, Rac, and Cdc42 with adenosine 5'-monophosphate (AMP). The resulting AMPylation prevented the interaction of Rho GTPases with downstream effectors, thereby inhibiting actin assembly in the infected cell. Eukaryotic proteins were also directly modified with AMP, potentially expanding the repertoire of posttranslational modifications for molecular signaling.
authors.affiliation: Department of Molecular Biology, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Yarbrough
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Kinch
authors.forename: Nick V
authors.initials: NV
authors.lastname: Grishin
authors.forename: Haydn L
authors.initials: HL
authors.lastname: Ball
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D048430:Cell Shape; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D014736:Vibrio parahaemolyticus / Q000378:metabolism* / Q000472:pathogenicity; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D013912:Threonine; D000249:Adenosine Monophosphate; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins