Characterization of the Type III Effector VOPA from Vibrio Parahaemolyticus

Vibrio parahaemolyticus is a marine bacterium and causative agent of gastroenteritis associated with the consumption of contaminated seafood. It is endemic to Southeast Asia and is the leading cause of gastroenteritis in Japan. Sequencing of the Vibrio parahaemolyticus genome revealed the presence of a type III secretion system (TTSS) encoded within a pathogenicity island. Within this pathogenicity island a homologue of the Yersinia type III effector YopJ was found and is referred to as VopA (Vibrio outer protein A). The founding member of the family, YopJ from Yersinia spp., inhibits the MAPK and the NFκB signaling cascades within the host cell, thereby inhibiting the host's innate immune response. Recently our lab elucidated the mechanism of YopJ's inhibition by demonstrating that YopJ acetylates MKKs and inhibits kinase activation by blocking phosphorylation (1). The molecular characterization of VopA has focused on its effect on signaling pathways. In contrast to YopJ, VopA only inhibits MAPK signaling and shows no effect on the NFκB pathway in mammalian cells. In addition, VopA, like YopJ, utilizes an evolutionary conserved mechanism for inhibition of signaling which is demonstrated by VopA's ability to inhibit MAPK signaling in Saccharo ces cerevisiae. I have shown that VopA is an acetyltransferase targets the MKK within the MAPK cascade revealing an activity similar to YopJ's. Through mass spectrometric analysis, I found that VopA modifies MKK on four different residues. Three of the residues, S207, K210, and T211, that are located in the activation loop, are the same residues modified by YopJ. The fourth residue, K172, is only modified by VopA and is a conserved lysine in the catalytic loop of MKKs that is required for ATP binding. I have shown that VopA's modification of this residue disrupts ATP binding and allows for the inhibition of an activated kinase.

Author dc:creator

• Trosky, Jennifer E.

Contributors dc:contributor

• Orth, Kim

• Vibrio parahaemolyticus
• Mitogen-Activated Protein Kinase Kinases
• Bacterial Toxins

Language dc:language

en

Identifier

759398969

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/770