title: Structural basis for the molecular evolution of SRP-GTPase activation by protein.
abstract: Small G proteins have key roles in signal transduction pathways. They are switched from the signaling 'on' to the non-signaling 'off' state when GTPase-activating proteins (GAPs) provide a catalytic residue. The ancient signal recognition particle (SRP)-type GTPases form GTP-dependent homo- and heterodimers and deviate from the canonical switch paradigm in that no GAPs have been identified. Here we show that the YlxH protein activates the SRP-GTPase FlhF. The crystal structure of the Bacillus subtilis FlhF-effector complex revealed that the effector does not contribute a catalytic residue but positions the catalytic machinery already present in SRP-GTPases. We provide a general concept that might also apply to the RNA-driven activation of the universally conserved, co-translational protein-targeting machinery comprising the SRP-GTPases Ffh and FtsY. Our study exemplifies the evolutionary transition from RNA- to protein-driven activation in SRP-GTPases and suggests that the current view on SRP-mediated protein targeting is incomplete.
authors: Heidelberg University Biochemistry Center, Heidelberg, Germany. gert.bange@bzh.uni-heidelberg.de
authors: Gert
authors: G
authors: Bange
authors: Nico
authors: N
authors: Kümmerer
authors: Przemyslaw
authors: P
authors: Grudnik
authors: Robert
authors: R
authors: Lindner
authors: Georg
authors: G
authors: Petzold
authors: Dieter
authors: D
authors: Kressler
authors: Ed
authors: E
authors: Hurt
authors: Klemens
authors: K
authors: Wild
authors: Irmgard
authors: I
authors: Sinning
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; C078317:flhF protein, Bacteria; D020559:Monomeric GTP-Binding Proteins