title: Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation.
abstract: The Salmonella typhimurium type III secretion effector protein SifA is essential for inducing tubulation of the Salmonella phagosome and binds the mammalian kinesin-binding protein SKIP. Coexpression of SifA with the effector SseJ induced tubulation of mammalian cell endosomes, similar to that induced by Salmonella infection. Interestingly, GTP-bound RhoA, RhoB, and RhoC also induced endosomal tubulation when coexpressed with SseJ, indicating that SifA likely mimics or activates a RhoA family GTPase. The structure of SifA in complex with the PH domain of SKIP revealed that SifA has two distinct domains; the amino terminus binds SKIP, and the carboxyl terminus has a fold similar to SopE, a Salmonella effector with Rho GTPase guanine nucleotide exchange factor activity (GEF). Similar to GEFs, SifA interacted with GDP-bound RhoA, and purified SseJ and RhoA formed a protein complex, suggesting that SifA, SKIP, SseJ, and RhoA family GTPases cooperatively promote host membrane tubulation.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Maikke B
authors.initials: MB
authors.lastname: Ohlson
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
authors.forename: Neal M
authors.initials: NM
authors.lastname: Alto
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Blanc
authors.forename: Jack E
authors.initials: JE
authors.lastname: Dixon
authors.forename: Jijie
authors.initials: J
authors.lastname: Chai
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012480:Salmonella Infections / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006023:Glycoproteins; C421862:SifA protein, Salmonella; C103987:SopE protein, Salmonella; C471548:SKIP enzyme, human; D010744:Phosphoric Monoester Hydrolases; D020741:rho GTP-Binding Proteins