Structural basis for the molecular evolution of SRP-GTPase activation by protein

Nat Struct Mol Biol. 2011 Nov 6;18(12):1376-80. doi: 10.1038/nsmb.2141.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacillus subtilis / enzymology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology
  • Crystallography, X-Ray
  • Enzyme Activation
  • Evolution, Molecular*
  • Models, Molecular
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins / chemistry*
  • Monomeric GTP-Binding Proteins / metabolism
  • Monomeric GTP-Binding Proteins / physiology
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Signal Transduction


  • Bacterial Proteins
  • flhF protein, Bacteria
  • Monomeric GTP-Binding Proteins

Associated data

  • PDB/3SYN