GTP-binding and association of the Escherichia coli signal recognition particle protein, Ffh, and its receptor, FtsY

Kelly M. Elkins*¹, Irmgard Sinning², and Rebecca C. Wade¹

*email: kelly.elkins@eml.villa-bosch.de

¹European Media Laboratory, Schloss-Wolfsbrunnenweg 33, D-69118 Heidelberg, Germany

²Biochemiezentrum (BZH), Universitaet Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany

Abstract: The signal recognition particle (SRP) is a universally conserved system for protein trafficking. Many SRPs are GTP-binding proteins. Their crucial role in ensuring that proteins are not misplaced into the wrong cellular location makes them potential targets for drug design. The aim of our work is to derive structural models of the interactions of the SRP and its receptor. This is being done for the SRP system from Escherichia coli, which is much simpler than that found in humans and thus provides a good model system. The E. coli SRP is a ribonucleoprotein complex composed of a 48 kDa GTPase protein and a 4.5 S RNA. While the crystal structure of the E. coli SRP receptor FtsY, also a GTPase, has been solved, the structure of the E. coli SRP protein itself has not. Consequently, we have used comparative modelling techniques to build a model of the E. coli SRP protein, Ffh, on the basis of SRP structures from other organisms and to dock GTP and Mg²⁺ into their hypothesized sites on both Ffh and FtsY. These modelled structures are being used to build a model of the active SRP:SRP receptor complex. This model should prove useful in understanding how the components of the SRP interact to direct protein traffic within and out of the cell.