The ribosome regulates the GTPase of the β-subunit of the signal recognition particle receptor

Protein targeting to the membrane of the ER is regulated by three GTPases, the 54-kD subunit of the signal recognition particle (SRP) and the alpha- and beta-subunit of the SRP receptor (SR). Here, we report on the GTPase cycle of the beta-subunits of the SR (SR beta),We found that SR beta binds GTP with high affinity and interacts with ribosomes in the GTP-bound state. Subsequently, the ribosome increases the GTPase activity of SR beta and thus functions as a GTPase activating protein for SR beta. Furthermore, the interaction between SR beta and the ribosome leads to a reduction in the affinity of SR beta for guanine nucleotides. We propose that SR beta regulates the interaction of SR with the ribosome and thereby allows SR alpha to scan membrane-bound ribosomes for the presence of SRP, Interaction between SRP and SR alpha then leads to release of the signal sequence from SRP and insertion into the translocon, GTP hydrolysis then results in dissociation of SR from the ribosome, and SRP from the SR.