Interaction of E. coli Ffh/4.5S ribonucleoprotein and FtsY mimics that of mammalian signal recognition particle and its receptor

Abstract

THE mechanism of protein translocation across the endoplasmic reticulum membrane of eukaryotic cells and the plasma membrane of prokaryotic cells are thought to be evolutionarily related^1–7. Protein targeting to the eukaryotic translocation apparatus is mediated by the signal recognition particle (SRP), a cytosolic ribonucleoprotein, and the SRP receptor, an endoplasmic reticulum membrane protein^8,9. During targeting, the 54K SRP subunit (M_r 54,000; SRP54), a GTP-binding protein^10–12, binds to signal sequences^13,14 and then interacts with the α-subunit of the SRP receptor (SRα), another GTP-binding protein^12,15. Two proteins from Escherichia coli, Ffh and FtsY, structurally resemble SRP54 and SRα^10,11,16. Like SRP54, Ffh is a subunit of a cytosolic ribonucleoprotein that also contains the E. coli 4.5S RNA^17,18. Although there is genetic and biochemical evidence that the E. coli Ffh/4.5S ribonucleoprotein has an SRP-like function^19–21, there is no evidence for an SRα-like role for FtsY. Here we show that the Ffh/4.5S ribonucleoprotein binds tightly to FtsY in a GTP-dependent manner. This interaction results in the stimulation of GTP hydrolysis which can be inhibited by synthetic signal peptides. These properties mimic those of mammalian SRP and its receptor, suggesting that the E. coli Ffh/4.5S ribonucleoprotein and FtsY have functions in protein targeting that are similar to those of their mammalian counterparts.