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bioRxiv · 10.1101/2023.12.21.572903

Cryo-EM structure of the bacterial effector protein SipA bound to F-actin reveals a unique mechanism for filament stabilization

Guo, E.·Chou, S. Z.·Lara-Tejero, M.·Galan, J. E.
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Abstract

The bacterial pathogen Salmonella spp. modulates cellular processes by delivering effector proteins through its type III secretion systems. Among these effectors, SipA facilitates bacterial invasion and promotes intestinal inflammation. The mechanisms by which this effector carries out these functions are incompletely understood, although SipAs ability to modulate actin dynamics is central to some of these activities. Here, we report the cryo-EM structure of SipA bound to filamentous actin. The structure shows that this effector stabilizes actin filaments through unique interactions of its carboxy-terminal domain with four actin subunits. Furthermore, our structure-function studies revealed that SipAs actin-binding activity is independent of its ability to stimulate intestinal inflammation. Overall, these studies illuminate critical aspects of Salmonella pathogenesis and provide unique insight into the mechanisms by which a bacterial effector modulates actin dynamics.

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Guo, E., Chou, S. Z., Lara-Tejero, M., Galan, J. E.. 2023-12-22. Cryo-EM structure of the bacterial effector protein SipA bound to F-actin reveals a unique mechanism for filament stabilization. https://doi.org/10.1101/2023.12.21.572903

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