The crystal structure of the conserved GTPase of SRP54 from the archaeon Acidianus ambivalens and its comparison with related structures suggests a model for the SRP-SRP receptor complex

Background: Protein targeting to the endoplasmic reticulum in eukaryotes an d to the cell membrane in prokaryotes is mediated by the signal recognition particle (SRP) and its receptor (SR). Both contain conserved GTPase domain s in the signal-peptide-binding proteins (SRP54 and Ffh) and the SR protein s (SR alpha and FtsY). These GTPases are involved in the regulation of prot ein targeting. Most studies so far have focussed on the SRP machinery of ma mmals and bacteria, leaving the SRP system of archaea less well understood. Results: We report the crystal structure of the conserved GTPase (NG-Ffh) f rom the thermophilic archaeon Acidianus ambivalens at 2.0 Angstrom resoluti on and of the Thr112-->Ala mutant, which is inactive in GTP hydrolysis. Thi s is the first structure of an SRP component from an archaeon and allows fo r a detailed comparison with related structures from Escherichia coli and t hermophilic bacteria. In particular, differences in the conserved consensus regions for nucleotide binding and the subdomain interfaces are observed, which provide information about the regulation of the GTPase. These interac tions allow us to propose a common signalling mechanism for the SRP-SR syst em. Conclusions: The overall structure of SRP-GTPases is well conserved between bacteria and archaea, which indicates strong similarities in the regulatio n of the SRP-targeting pathway. Surprisingly, structure comparisons identif ied a homodimeric ATP-binding protein as the closest relative. A heterodime r model for the SRP-SR interaction is presented.