Editors' ChoiceHost-Pathogen Interactions

A little toxin can do a lot

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Science Signaling  04 Aug 2015:
Vol. 8, Issue 388, pp. ec222
DOI: 10.1126/scisignal.aad1355

The actin cross-linking domain (ACD) is an actin-specific toxin produced by several bacterial pathogens. Heisler et al. discovered that ACD's pathogenic mechanism involves a highly unusual toxicity amplification cascade. Rather than directly inactivating the actin cytoskeleton, ACD blocks the activity of formins, actin regulatory proteins that play crucial roles in numerous cellular activities. ACD is exceptionally potent, even though its substrate is actin, the most abundant protein of a eukaryotic cell.

D. B. Heisler, E. Kudryashova, D. O. Grinevich, C. Suarez, J. D. Winkelman, K. G. Birukov, S. R. Kotha, N. L. Parinandi, D. Vavylonis, D. R. Kovar, D. S. Kudryashov, ACD toxin–produced actin oligomers poison formin-controlled actin polymerization. Science 349, 535–539 (2015). [Abstract] [Full Text]