Structural highlights
Function
[SOPD2_SALTY] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. Contributes to the formation of Salmonella-induced filaments (Sifs) in infected epithelial cells and to replication in macrophages.[1]
Publication Abstract from PubMed
Intracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target.
Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7.,D'Costa VM, Braun V, Landekic M, Shi R, Proteau A, McDonald L, Cygler M, Grinstein S, Brumell JH Cell Rep. 2015 Sep 1;12(9):1508-18. doi: 10.1016/j.celrep.2015.07.063. Epub 2015 , Aug 20. PMID:26299973[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jiang X, Rossanese OW, Brown NF, Kujat-Choy S, Galan JE, Finlay BB, Brumell JH. The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice. Mol Microbiol. 2004 Dec;54(5):1186-98. PMID:15554961 doi:http://dx.doi.org/10.1111/j.1365-2958.2004.04344.x
- ↑ D'Costa VM, Braun V, Landekic M, Shi R, Proteau A, McDonald L, Cygler M, Grinstein S, Brumell JH. Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7. Cell Rep. 2015 Sep 1;12(9):1508-18. doi: 10.1016/j.celrep.2015.07.063. Epub 2015 , Aug 20. PMID:26299973 doi:http://dx.doi.org/10.1016/j.celrep.2015.07.063