Abstract
SipA is a Salmonella protein delivered into host cells to promote efficient bacterial entry, which is essential for pathogenicity. SipA exerts its function by binding F-actin, resulting in the stabilization of F-actin and the stimulation of the bundling activity of fimbrin. Here we show that under low salt conditions where spontaneous nucleation and polymerization of actin do not occur, SipA induces extensive polymerization. We have used electron microscopy and a method for helical image analysis to visualize the complex of actin with the actin-binding fragment of SipA. The SipA fragment binds to actin as a tubular molecule extending ∼95 Å. The main sites of SipA binding on actin involve sequence insertions that are not present in the bacterial homolog of actin, MreB, suggesting a mechanism for preventing SipA from interacting with bacterial MreB filaments. Remarkably, the pattern of SipA binding, which connects subunits on opposite actin strands and explains the stabilization of F-actin, is similar to that shown for a fragment of the giant muscle protein nebulin. We suggest that SipA is a bacterial structural mimic of muscle nebulin and nebulin-like proteins in non-muscle cells that are involved in the regulation of the actin-based cytoskeleton.
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References
Galan, J.E. Annu. Rev. Cell Dev. Biol. 17, 53–86 (2001).
Mitra, K., Zhou, D. & Galan, J.E. FEBS Lett. 482, 81–84 (2000).
Zhou, D., Mooseker, M.S. & Galan, J.E. Science 283, 2092–2095 (1999).
Zhou, D., Mooseker, M.S. & Galan, J.E. Proc. Natl. Acad. Sci. USA 96, 10176–10181 (1999).
Egelman, E.H. Ultramicroscopy 85, 225–234 (2000).
Lukoyanova, N. et al. Curr. Biol. 12, 383–388 (2002).
Orlova, A. et al. J. Mol. Biol. 312, 95–106 (2001).
Galkin, V.E., Orlova, A., Lukoyanova, N., Wriggers, W. & Egelman, E.H. J. Cell Biol. 153, 75–86 (2001).
Galkin, V.E. et al. J. Cell Biol. 157, 243–251 (2002).
Berger, B. et al. Proc. Natl. Acad. Sci. USA 92, 8259–8263 (1995).
Wang, K. et al. J. Biol. Chem. 271, 4304–4314 (1996).
Gonsior, S.M., Gautel, M. & Hinssen, H. J. Muscle Res. Cell Motil. 19, 225–235 (1998).
Chen, M.J., Shih, C.L. & Wang, K. J. Biol. Chem. 268, 20327–20334 (1993).
Schreiber, V. et al. Gene 207, 171–175 (1998).
Chew, C.S., Parente, J.A. Jr, Chen, X., Chaponnier, C. & Cameron, R.S. J. Cell Sci. 113, 2035–2045 (2000).
Stebbins, C.E. & Galan, J.E. Nature 412, 701–705 (2001).
van den Ent, F., Amos, L.A. & Lowe, J. Nature 413, 39–44 (2001).
Egelman, E.H. Curr. Biol. 11, R1022–R1024 (2001).
Jones, L.J., Carballido-Lopez, R. & Errington, J. Cell 104, 913–922 (2001).
Acknowledgements
This work was supported by NIH grants (to E.H.E. and to J.E.G.).
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Galkin, V., Orlova, A., VanLoock, M. et al. The bacterial protein SipA polymerizes G-actin and mimics muscle nebulin. Nat Struct Mol Biol 9, 518–521 (2002). https://doi.org/10.1038/nsb811
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DOI: https://doi.org/10.1038/nsb811
