Molecular evolution of SRP-GTPase activation by protein

Small G proteins play key roles in signal transduction pathways and act as molecular switches, which cycle between the signalling ‘on’ and the non-signalling ‘off’ state. GTPase activating proteins (GAPs) provide a catalytic residue, which completes that catalytic machinery to allow efficient GTP hydrolysis. Signal recognition particle (SRP)-type GTPases are essential for protein targeting and constitute a distinct subfamily with only three members. They form GTP-dependent homo-and heterodimers and deviate from the canonical switch paradigm as no GAPs have been reported. Here we identify a SRP GTPase activating protein and present the crystal structure of the SRP-GTPase/effector complex. The activator does not contribute a catalytic residue, but positions the catalytic machinery already present in SRP GTPases. Our study exemplifies the evolutionary transition from RNA- to protein-driven activation in SRP-GTPases.