The Ribosome Regulates the Gtpase of the β-Subunit of the Signal Recognition Particle Receptor

Abstract

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 α- and β-subunit of the SRP receptor (SR). Here, we report on the GTPase cycle of the β-subunits of the SR (SRβ). We found that SRβ binds GTP with high affinity and interacts with ribosomes in the GTP-bound state. Subsequently, the ribosome increases the GTPase activity of SRβ and thus functions as a GTPase activating protein for SRβ. Furthermore, the interaction between SRβ and the ribosome leads to a reduction in the affinity of SRβ for guanine nucleotides. We propose that SRβ regulates the interaction of SR with the ribosome and thereby allows SRα to scan membrane-bound ribosomes for the presence of SRP. Interaction between SRP and SRα 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.