Signal Sequences Activate the Catalytic Switch of SRP RNA

The signal recognition particle ( SRP) recognizes polypeptide chains bearing a signal sequence as they emerge from the ribosome, and then binds its membrane- associated receptor ( SR), thereby delivering the ribosome- nascent chain complex to the endoplasmic reticulum in eukaryotic cells and the plasma membrane in prokaryotic cells. SRP RNA catalytically accelerates the interaction of SRP and SR, which stimulates their guanosine triphosphatase ( GTPase) activities, leading to dissociation of the complex. We found that although the catalytic activity of SRP RNA appeared to be constitutive, SRP RNA accelerated complex formation only when SRP was bound to a signal sequence. This crucial control step was obscured because a detergent commonly included in the reaction buffer acted as a signal peptide mimic. Thus, SRP RNA is a molecular switch that renders the SRP- SR GTPase engine responsive to signal peptide recruitment, coupling GTP hydrolysis to productive protein targeting.