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Published on: April 17, 2014
Salmonella SipA polymerizes actin by stapling filaments with nonglobular protein arms
Mirjana Lilic1, Vitold E Galkin, Albina Orlova
1Laboratory of Structural Microbiology, Rockefeller University, New York, NY 10021, USA.
Abstract:
Like many bacterial pathogens, Salmonella spp. use a type III secretion system to inject virulence proteins into host cells. The Salmonella invasion protein A (SipA) binds host actin, enhances its polymerization near adherent extracellular bacteria, and contributes to cytoskeletal rearrangements that internalize the pathogen. By combining x-ray crystallography of SipA with electron microscopy and image analysis of SipA-actin filaments, we show that SipA functions as a "molecular staple," in which a globular domain and two nonglobular "arms" mechanically stabilize the filament by tethering actin subunits in opposing strands. Deletion analysis of the tethering arms provides strong support for this model.
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