Nucleotide-dependent binding of the GTPase domain of the signal recognition particle receptor beta-subunit to the alpha-subunit

The signal recognition particle (SRP) receptor (SR) is a heterodimer of two polypeptides (SR alpha and SR beta) that each contain a GTP-binding. domai n. The GTP-binding domain in the peripheral membrane SR alpha subunit has a well defined role in regulating targeting of SRP-ribosome-nascent chain co mplexes to the translocon. The only well established function for the trans membrane SRP subunit is anchoring SR alpha On the endoplasmic reticulum mem brane. Deletion of the amino-terminal transmembrane domain of SRP did not a ffect receptor dimerization, but revealed a cryptic translocation signal th at overlaps the GTPase domain. We demonstrate that the domain of SRa that b inds SRP does so by binding directly to the nucleotide-bound form of the GT Pase domain of SR beta. An SR beta mutant containing an amino acid substitu tion that allows the GTPase domain to bind XTP dimerized with SRa most effi ciently 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.