title: Lipids trigger a conformational switch that regulates signal recognition particle (SRP)-mediated protein targeting.
abstract: Co-translational protein targeting to the membrane is mediated by the signal recognition particle and its receptor (FtsY). Their homologous GTPase domains interact at the membrane and form a heterodimer in which both GTPases are activated. The prerequisite for protein targeting is the interaction of FtsY with phospholipids. However, the mechanism of FtsY regulation by phospholipids remained unclear. Here we show that the N terminus of FtsY (A domain) is natively unfolded in solution and define the complete membrane-targeting sequence. We show that the membrane-targeting sequence is highly dynamic in solution, independent of nucleotides and directly responds to the density of anionic phospholipids by a random coil-helix transition. This conformational switch is essential for tethering FtsY to membranes and activates the GTPase for its subsequent interaction with the signal recognition particle. Our results underline the dynamics of lipid-protein interactions and their importance in the regulation of protein targeting and translocation across biological membranes.
authors.affiliation: Biochemie Zentrum (BZH), University of Heidelberg, INF 328, 69120 Heidelberg, Germany.
authors.forename: Goran
authors.initials: G
authors.lastname: Stjepanovic
authors.forename: Katja
authors.initials: K
authors.lastname: Kapp
authors.forename: Gert
authors.initials: G
authors.lastname: Bange
authors.forename: Christian
authors.initials: C
authors.lastname: Graf
authors.forename: Richard
authors.initials: R
authors.lastname: Parlitz
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Mayer
authors.forename: Irmgard
authors.initials: I
authors.lastname: Sinning
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C087406:FtsY protein, Bacteria; D010743:Phospholipids; D018160:Receptors, Cytoplasmic and Nuclear; D018271:Signal Recognition Particle; D020558:GTP Phosphohydrolases