Nucleotide-dependent Binding of the GTPase Domain of the Signal Recognition Particle Receptor β-Subunit to the α-Subunit

The signal recognition particle (SRP) receptor (SR) is a heterodimer of two polypeptides (SRα and SRβ) that each contain a GTP-binding domain. The GTP-binding domain in the peripheral membrane SRα subunit has a well defined role in regulating targeting of SRP-ribosome-nascent chain complexes to the translocon. The only well established function for the transmembrane SRβ subunit is anchoring SRα on the endoplasmic reticulum membrane. Deletion of the amino-terminal transmembrane domain of SRβ did not affect receptor dimerization, but revealed a cryptic translocation signal that overlaps the GTPase domain. We demonstrate that the domain of SRα that binds SRβ does so by binding directly to the nucleotide-bound form of the GTPase domain of SRβ. An SRβ mutant containing an amino acid substitution that allows the GTPase domain to bind XTP dimerized with SRα most efficiently in the presence of XTP or XDP, but not ATP. Our results suggest an additional level of regulation of SRP receptor function based on regulated dissociation of the receptor subunits.