G. Bacher et al., REGULATION BY THE RIBOSOME OF THE GTPASE OF THE SIGNAL-RECOGNITION PARTICLE DURING PROTEIN TARGETING, Nature, 381(6579), 1996, pp. 248-251
THE signal-recognition particle (SRP) is important for the targeting o
f many secretory and membrane proteins to the endoplasmic reticulum (E
R). Targeting is regulated by three GTPases, the 54K subunit of SRP (S
RP54), and the alpha- and beta-subunits of the SRP receptor(1). When a
signal sequence emerges from the ribosome, SRP interacts with it and
targets the resulting complex to the ER membrane by binding to the SRP
receptor. Subsequently, SRP releases the signal sequence into the tra
nslocation channel(2,3). Here we use a complex of a ribosome with a na
scent peptide chain, the SRP and its receptor, to investigate GTP bind
ing to SRP54, and GTP hydrolysis. Our findings indicate that a ribosom
al component promotes GTP binding to the SRP54 subunit of SRP, GTP-bou
nd SRP54 is essential for high-affinity interaction between SRP and it
s receptor in the ER membrane. This interaction induces the release of
the signal sequence from SRP, the insertion of the nascent polypeptid
e chain into the translocation channel, and GTP hydrolysis. The contri
bution of the ribosome had previously escaped detection because only s
ynthetic signal peptides were used in the analysis(4).