SR beta coordinates signal sequence release from SRP with ribosome bindingto the translocon

Protein targeting to the endoplasmic reticulum (ER) membrane is regulated b y 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 s oluble form of SR and an XTP-binding mutant of SR beta, we show that SR bet a 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 si gnal sequence release from SRP. This is achieved by the presence of the tra nslocon, 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 be ta co-ordinates the release of the signal sequence from SRP with the presen ce of the translocon.