3eb8

Structural highlights

Function

[VIRA_SHIFL] Alpha-tubulin-specific protease that is required for entry into epithelial cells and for subsequent intra- and intercellular spreading. Contributes to bacterial entry into epithelial cells by inducing microtubule (MT) destabilization and the formation of membrane ruffles. The membrane ruffling evoked by VirA results from the activation of host rac1, which is associated with the destruction of MT networks. Creates a tunnel inside the host cell cytoplasm by breaking down the microtubule infrastructure. This facilitates the bacterium's movement through the cytoplasm and also helps other bacteria move faster during the invasion of the eukaryotic cell. Is absolutely required for virulence.^{[1] [2] [3]}

References

1. ↑ Uchiya K, Tobe T, Komatsu K, Suzuki T, Watarai M, Fukuda I, Yoshikawa M, Sasakawa C. Identification of a novel virulence gene, virA, on the large plasmid of Shigella, involved in invasion and intercellular spreading. Mol Microbiol. 1995 Jul;17(2):241-50. PMID:7494473
2. ↑ Yoshida S, Katayama E, Kuwae A, Mimuro H, Suzuki T, Sasakawa C. Shigella deliver an effector protein to trigger host microtubule destabilization, which promotes Rac1 activity and efficient bacterial internalization. EMBO J. 2002 Jun 17;21(12):2923-35. PMID:12065406 doi:10.1093/emboj/cdf319
3. ↑ Yoshida S, Handa Y, Suzuki T, Ogawa M, Suzuki M, Tamai A, Abe A, Katayama E, Sasakawa C. Microtubule-severing activity of Shigella is pivotal for intercellular spreading. Science. 2006 Nov 10;314(5801):985-9. PMID:17095701 doi:10.1126/science.1133174
4. ↑ Germane KL, Ohi R, Goldberg MB, Spiller BW. Structural and functional studies indicate that Shigella VirA is not a protease and does not directly destabilize microtubules. Biochemistry. 2008 Sep 30;47(39):10241-3. Epub 2008 Sep 3. PMID:18763811 doi:10.1021/bi801533k