The pathogen protein EspF(U) hijacks actin polymerization using mimicry and multivalency. Academic Article uri icon


  • Enterohaemorrhagic Escherichia coli attaches to the intestine through actin pedestals that are formed when the bacterium injects its protein EspF(U) (also known as TccP) into host cells. EspF(U) potently activates the host WASP (Wiskott-Aldrich syndrome protein) family of actin-nucleating factors, which are normally activated by the GTPase CDC42, among other signalling molecules. Apart from its amino-terminal type III secretion signal, EspF(U) consists of five-and-a-half 47-amino-acid repeats. Here we show that a 17-residue motif within this EspF(U) repeat is sufficient for interaction with N-WASP (also known as WASL). Unlike most pathogen proteins that interface with the cytoskeletal machinery, this motif does not mimic natural upstream activators: instead of mimicking an activated state of CDC42, EspF(U) mimics an autoinhibitory element found within N-WASP. Thus, EspF(U) activates N-WASP by competitively disrupting the autoinhibited state. By mimicking an internal regulatory element and not the natural activator, EspF(U) selectively activates only a precise subset of CDC42-activated processes. Although one repeat is able to stimulate actin polymerization, we show that multiple-repeat fragments have notably increased potency. The activities of these EspF(U) fragments correlate with their ability to coordinate activation of at least two N-WASP proteins. Thus, this pathogen has used a simple autoinhibitory fragment as a component to build a highly effective actin polymerization machine.

published proceedings

  • Nature

altmetric score

  • 4

author list (cited authors)

  • Sallee, N. A., Rivera, G. M., Dueber, J. E., Vasilescu, D., Mullins, R. D., Mayer, B. J., & Lim, W. A.

citation count

  • 96

complete list of authors

  • Sallee, Nathan A||Rivera, Gonzalo M||Dueber, John E||Vasilescu, Dan||Mullins, R Dyche||Mayer, Bruce J||Lim, Wendell A

publication date

  • January 2008

published in