Structure of the conserved GTPase domain of the signal recognition particle

Nature. 1997 Jan 23;385(6614):361-4. doi: 10.1038/385361a0.


The signal-recognition particle (SRP) and its receptor (SR) function in the co-translational targeting of nascent protein-ribosome complexes to the membrane translocation apparatus. The SRP protein subunit (termed Ffh in bacteria) that recognizes the signal sequence of nascent polypeptides is a GTPase, as is the SR-alpha subunit (termed FtsY). Ffh and FtsY interact directly, each stimulating the GTP hydrolysis activity of the other. The sequence of Ffh suggests three domains: an amino-terminal N domain of unknown function, a central GTPase G domain, and a methionine-rich M domain that binds both SRP RNA and signal peptides. Sequence conservation suggests that structurally similar N and G domains are present in FtsY. Here we report the structure of the nucleotide-free form of the NG fragment of Ffh. Consistent with a role for apo Ffh in protein targeting, the side chains of the empty active-site pocket form a tight network of interactions which may stabilize the nucleotide-free protein. The structural relationship between the two domains suggests that the N domain senses or controls the nucleotide occupancy of the GTPase domain. A structural subdomain unique to these evolutionarily conserved GTPases constitutes them as a distinct subfamily in the GTPase superfamily.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Binding Sites
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Electrochemistry
  • Escherichia coli Proteins*
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • Models, Molecular
  • Protein Conformation*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Signal Recognition Particle / chemistry*
  • Signal Recognition Particle / genetics
  • Thermus / enzymology


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Ffh protein, E coli
  • Recombinant Proteins
  • Signal Recognition Particle
  • GTP Phosphohydrolases