Mapping the selection mechanisms by bacterial GEFs

Mimicry of eukaryotic signaling enzymes is a common strategy used by bacterial pathogens to manipulate host cellular signaling. The E. coli type III effector protein Map belongs to a large family of bacterial virulence factors that activate host Rho GTPase signaling pathways through an unknown molecular mechanism. Our recent structural study, coupled with biochemical and functional assays, establishes that this family protein, including Map, IpgB1/2 and SifA/B secreted by E. coli, Shigella, and Salmonella respectively, acts as functional mimic of mammalian guanine nucleotide exchange factors (GEFs). Furthermore, we show that Map and its family members share a conserved mechanism with human Dbl GEFs for selection of various GTPase isoforms, revealing an evolutionary dynamic state of protein mimicry.