Structure of Shigella IpgB2 in Complex with Human RhoA IMPLICATIONS FOR THE MECHANISM OF BACTERIAL GUANINE NUCLEOTIDE EXCHANGE FACTOR MIMICRY

摘要: A common theme in bacterial pathogenesis is the manipulation of eukaryotic cells by targeting cytoskeleton. This most cases achieved either modifying actin, or indirectly via activation key regulators controlling actin dynamics such as Rho-GTPases. novel group virulence factors termed WXXXE family has emerged guanine nucleotide exchange (GEFs) for these GTPases. The precise mechanism exchange, however, remained unclear. Here we report structure WXXXE-protein IpgB2 from Shigella flexneri and its complex with human RhoA. We unambiguously identify a RhoA-GEF dissect molecular GDP release, an essential prerequisite GTP binding. Our observations uncover that induces conformational changes on RhoA mimicking DbI- but not DOCK GEFs. also show dissociation GDP·Mg2+ preceded displacement metal ion to α-phosphate nucleotide, diminishing affinity GTPase. These data refine our understanding mode action only GEFs mammalian DH/PH family.