SRβ coordinates signal sequence release from SRP with ribosome binding to the translocon

Protein targeting to the endoplasmic reticulum (ER) membrane is regulated by three GTPases, the 54 kDa subunit of the signal recognition particle (SR beta) and the alpha- and beta -subunits of the SRP receptor (SR). Using a soluble form of SR and an XTP-binding mutant of SR beta, we show that SR beta is essential for protein translocation across the ER membrane. SRP can be cross-linked to 21 kDa ribosomal protein in its empty and GDP-bound state, but not when GTP is bound. GTP binding to SR beta is required to induce signal sequence release from SRP. This is achieved by the presence of the translocon, which changes the interaction between the 21 kDa ribosomal protein and SR beta and thereby allows SR beta to bind GTP. We conclude that SR beta co-ordinates the release of the signal sequence from SRP with the presence of the translocon.