BINDING OF SIGNAL RECOGNITION PARTICLE GIVES RIBOSOME NASCENT CHAIN COMPLEXES A COMPETITIVE ADVANTAGE IN ENDOPLASMIC-RETICULUM MEMBRANE INTERACTION/

Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the bi nding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP recepto r. However, ribosomes can also independently bind to the ER translocat ion channel formed by the Sec61p complex. To explain the specificity o f membrane targeting, it has therefore been proposed that nascent poly peptide-associated complex functions as a cytosolic inhibitor of signa l sequence- and SRP-independent ribosome binding to the ER membrane. W e report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect w hen SRP is bound to the RNCs. The protective effect of SRP against rib osome competition depends on a functional signal sequence in the nasce nt chain and is also observed with reconstituted proteoliposomes conta ining only the Sec61p complex and the SRP receptor. We conclude that c ytosolic factors do not prevent the membrane binding of ribosomes. Ins tead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP r eceptor, which gives RNC-SRP complexes a selective advantage in membra ne targeting over nontranslating ribosomes.