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- W2785363467 abstract "Intracellular pathogenic bacteria such as Salmonella or Shigella species manipulate host signaling pathways in order to survive and replicate. They secrete a cocktail of up to 30 virulence factors to the cytoplasm of their eukaryotic host cells using a so-called type III secretion system. Some virulence factors belong to conserved protein families, such as the WxxxE family to which the factors SifA and SifB from Salmonella sp. belong. Most factors of this family embody bacterial GEF-mimics that activate small GTPases of the Rho family in the host. However, no such activity was found for SifA and SifB. The aim of this study was to identify new molecular targets of these WxxxE effector proteins and characterize their interaction with signaling pathways in the host.In this study, I analyzed a number of promising candidates from a previous Y2H screen (Cep70/SifA, DYNLRB1/SifA, CLIP4/SifB) using biochemical and microscopic techniques. The main part of this work focuses on the novel interaction between the Salmonella WxxxE effector protein SifB and the host factor CLIP4, an as yet uncharacterized protein. The interaction surface between the two proteins was mapped to the C-terminal CAP-Gly-domains of CLIP4, which also mediate microtubule binding. SifB interacts specifically with CLIP4, but not with other members of the CAP-Gly-family such as CLIP1, -2 and -3. The data presented here suggest that CLIP4 is a microtubule binding- and bundling protein, which is found on interphase-microtubules of post-mitotic cells in selected tissues. In cultured cells the Salmonella effector protein SifB is distributed diffusely throughout the cytoplasm, but can be recruited to microtubules in the presence of CLIP4. In addition, SifB co-localizes together with CLIP4 at highly dynamic membrane tubules, so called SIFs (Salmonella-induced filaments), which are known to form along microtubules of infected cells. The data obtained here suggest that the host protein CLIP4 interacts with the bacterial virulence factor SifB, which is deposited by Salmonella at the SIF membrane and indirectly recruited to microtubules. This might contribute to anchoring of SIFs to microtubules during late stages of Salmonella infection. This is the first report of a direct interaction between a microtubule-binding host protein and a virulence factor from Salmonella." @default.
- W2785363467 created "2018-02-23" @default.
- W2785363467 creator A5022102967 @default.
- W2785363467 date "2016-01-01" @default.
- W2785363467 modified "2023-09-26" @default.
- W2785363467 title "Identification and characterization of interactions between bacterial WxxxE-virulence proteins and host cell proteins" @default.
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- W2785363467 doi "https://doi.org/10.24355/dbbs.084-201701051529-0" @default.
- W2785363467 hasPublicationYear "2016" @default.
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