| Structural highlights
Function
[SIFA_SALTY] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is required for endosomal tubulation and formation of Salmonella-induced filaments (Sifs), which are filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Sif formation is concomitant with intracellular bacterial replication.[1] [2] [3] [PKHM2_HUMAN] May play a role in the regulation of conventional kinesin activity. Required for maintenance of the Golgi apparatus organization. May play a role in membrane tubulation.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation.,Ohlson MB, Huang Z, Alto NM, Blanc MP, Dixon JE, Chai J, Miller SI Cell Host Microbe. 2008 Nov 13;4(5):434-46. PMID:18996344[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Brumell JH, Goosney DL, Finlay BB. SifA, a type III secreted effector of Salmonella typhimurium, directs Salmonella-induced filament (Sif) formation along microtubules. Traffic. 2002 Jun;3(6):407-15. PMID:12010459
- ↑ Boucrot E, Henry T, Borg JP, Gorvel JP, Meresse S. The intracellular fate of Salmonella depends on the recruitment of kinesin. Science. 2005 May 20;308(5725):1174-8. PMID:15905402 doi:308/5725/1174
- ↑ Ohlson MB, Huang Z, Alto NM, Blanc MP, Dixon JE, Chai J, Miller SI. Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe. 2008 Nov 13;4(5):434-46. PMID:18996344 doi:S1931-3128(08)00291-6
- ↑ Boucrot E, Henry T, Borg JP, Gorvel JP, Meresse S. The intracellular fate of Salmonella depends on the recruitment of kinesin. Science. 2005 May 20;308(5725):1174-8. PMID:15905402 doi:308/5725/1174
- ↑ Ohlson MB, Huang Z, Alto NM, Blanc MP, Dixon JE, Chai J, Miller SI. Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe. 2008 Nov 13;4(5):434-46. PMID:18996344 doi:S1931-3128(08)00291-6
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