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.
Bradshaw
Niels
N
Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
Neher
Saskia B
SB
Booth
David S
DS
Walter
Peter
P
D001426:Bacterial Proteins / Q000378:metabolism*; D055162:Biocatalysis; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D021382:Protein Sorting Signals; D012329:RNA, Bacterial / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000378:metabolism*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C087406:FtsY protein, Bacteria; D021382:Protein Sorting Signals; D012329:RNA, Bacterial; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C036318:signal peptide receptor; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases