A. Neuhof et al., BINDING OF SIGNAL RECOGNITION PARTICLE GIVES RIBOSOME NASCENT CHAIN COMPLEXES A COMPETITIVE ADVANTAGE IN ENDOPLASMIC-RETICULUM MEMBRANE INTERACTION/, Molecular biology of the cell, 9(1), 1998, pp. 103-115
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.