title: Activation of a bacterial virulence protein by the GTPase RhoA.
abstract: The Rho family of guanosine triphosphatases (GTPases) are essential eukaryotic signaling molecules that regulate cellular physiology. Virulence factors from various pathogens alter the signaling of GTPases by acting as GTPase activating factors, guanine nucleotide exchange factors, or direct covalent modifiers; however, bacterial virulence factors that sense rather than alter the signaling states of Rho GTPases have not been previously described. Here, we report that the translocated Salmonellae virulence factor SseJ binds to the guanosine triphosphate-bound form of RhoA. This interaction stimulates the lipase activity of SseJ, which results in the esterification of cholesterol in the host cell membrane. Our results suggest that the activation of molecules downstream of GTPases is not exclusive to eukaryotic proteins, and that a bacterial protein has evolved to recognize the activation state of RhoA, which regulates its enzymatic activity as part of the host-pathogen interaction.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Christen
authors.forename: Lisette H
authors.initials: LH
authors.lastname: Coye
authors.forename: Jill S
authors.initials: JS
authors.lastname: Hontz
authors.forename: Doris L
authors.initials: DL
authors.lastname: LaRock
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pfuetzner
authors.lastname: Megha
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D001426:Bacterial Proteins; D002784:Cholesterol / Q000378:metabolism; D004951:Esterification; D054884:Host-Pathogen Interactions; D006801:Humans; D008049:Lipase; D011485:Protein Binding; D012475:Salmonella; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D002784:Cholesterol; D008049:Lipase; D020742:rhoA GTP-Binding Protein