Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation.
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.
Ohlson
Maikke B
MB
Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Huang
Zhiwei
Z
Alto
Neal M
NM
Blanc
Marie-Pierre
MP
Dixon
Jack E
JE
Chai
Jijie
J
Miller
Samuel I
SI
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*
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