Salmonella SipA polymerizes actin by stapling filaments with nonglobular protein arms

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. laments, we show that SipA functions as a molecular staple, in which a globular domain and two nonglobular arms mechanically stabilize the. lament by tethering actin subunits in opposing strands. Deletion analysis of the tethering arms provides strong support for this model.