Anionic phospholipids are involved in membrane association of FtsY and stimulate its GTPase activity

FtsY, the Escherichia coli homologue of the eukaryotic signal recognition p article (SRP) receptor a-subunit, is located in both the cytoplasm and inne r membrane. It has been proposed that FtsY has a direct targeting function, but the mechanism of its association with the membrane is unclear. FtsY is composed of two hydrophilic domains: a highly charged N-terminal domain (t he A-domain) and a C-terminal GTP-binding domain (the NG-domain), FtsY does not contain any hydrophobic sequence that might explain its affinity for t he inner membrane, and a membrane-anchoring protein has not been detected, In this study, we provide evidence that FtsY interacts directly with E,coli phospholipids, with a preference for anionic phospholipids. The interactio n involves at least two lipid-binding sites, one of which is present in the NG-domain, Lipid association induced a conformational change in FtsY and g reatly enhanced its GTPase activity. We propose that lipid binding of FtsY is important for the regulation of SRP-mediated protein targeting.