The plague bacterium Yersinia pestis is closely related to Y. enterocolitica and Y. pseudotuberculosis, which are food-borne agents that cause inflammation of the stomach and intestines. All Yersinia bacteria have a virulence plasmid, which is necessary to cause disease. Plasmids are extra DNA molecules frequently found in bacteria containing genes that can be passed from one bacterial strain to another and that may confer an evolutionary advantage, such as antibiotic resistance.
In the case of Yersinia, the plasmid harbors numerous genes, including a large number that contribute to the ability of diverse pathogens to deliver virulence factors into host cells. One of these genes is YpkA, a protein with multiple domains, including one closely related to an enzyme, a type of kinase, not typically found in bacteria. Earlier studies found that mutations that eliminate this activity reduce but do not eliminate YpkA's ability to disrupt cell shape by modifying their cytoskeletal support system.
In the current study, the researchers solved the high-resolution crystal structure of a second YpkA domain, the "Rho-GTPase binding domain" along with the host protein, "Rac1," with which it interacts.
"The Yersinia structure was doing things to Rac1 that the host proteins normally do," Stebbins said, suggesting that the domain acted as a mimic.
Further examination confirmed the domain to be a mimic of mammalian "guanidine nucleotide dissociation inhibitor" (GDI) proteins with a critical role in the bacteria's ability to disrupt cell structure. The domain paralyzes cells by acting as an "off-switch" for host proteins involved in modify
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Source:Cell Press