Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 323 (5910): 127-130

Copyright © 2009 by the American Association for the Advancement of Science

Signal Sequences Activate the Catalytic Switch of SRP RNA

Niels Bradshaw,* Saskia B. Neher,* David S. Booth, Peter Walter{dagger}

Abstract: 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.

Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA, and Department of Biochemistry and Biophysics, University of California, Genentech Hall, MC 2200, 600 16th Street, San Francisco, CA 94158, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: pwalter{at}biochem.ucsf.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SRP RNA Remodeling by SRP68 Explains Its Role in Protein Translocation.
J. T. Grotwinkel, K. Wild, B. Segnitz, and I. Sinning (2014)
Science 344, 101-104
   Abstract »    Full Text »    PDF »
Structural insights of non-canonical U*U pair and Hoogsteen interaction probed with Se atom.
J. Sheng, J. Gan, A. S. Soares, J. Salon, and Z. Huang (2013)
Nucleic Acids Res. 41, 10476-10487
   Abstract »    Full Text »    PDF »
Fingerloop activates cargo delivery and unloading during cotranslational protein targeting.
A. R. Ariosa, S. S. Duncan, I. Saraogi, X. Lu, A. Brown, G. J. Phillips, and S.-O. Shan (2013)
Mol. Biol. Cell 24, 63-73
   Abstract »    Full Text »    PDF »
Evolution from the Prokaryotic to the Higher Plant Chloroplast Signal Recognition Particle: The Signal Recognition Particle RNA Is Conserved in Plastids of a Wide Range of Photosynthetic Organisms.
C. Trager, M. A. Rosenblad, D. Ziehe, C. Garcia-Petit, L. Schrader, K. Kock, C. Vera Richter, B. Klinkert, F. Narberhaus, C. Herrmann, et al. (2012)
PLANT CELL 24, 4819-4836
   Abstract »    Full Text »    PDF »
Translation Elongation Regulates Substrate Selection by the Signal Recognition Particle.
D. Zhang and S.-o. Shan (2012)
J. Biol. Chem. 287, 7652-7660
   Abstract »    Full Text »    PDF »
Signal sequence-independent SRP-SR complex formation at the membrane suggests an alternative targeting pathway within the SRP cycle.
D. Braig, M. Mircheva, I. Sachelaru, E. O. van der Sluis, L. Sturm, R. Beckmann, and H.-G. Koch (2011)
Mol. Biol. Cell 22, 2309-2323
   Abstract »    Full Text »    PDF »
Synergistic actions between the SRP RNA and translating ribosome allow efficient delivery of the correct cargos during cotranslational protein targeting.
K. Shen, X. Zhang, and S.-o. Shan (2011)
RNA 17, 892-902
   Abstract »    Full Text »    PDF »
The Crystal Structure of the Signal Recognition Particle in Complex with Its Receptor.
S. F. Ataide, N. Schmitz, K. Shen, A. Ke, S.-o. Shan, J. A. Doudna, and N. Ban (2011)
Science 331, 881-886
   Abstract »    Full Text »    PDF »
A Dynamic cpSRP43-Albino3 Interaction Mediates Translocase Regulation of Chloroplast Signal Recognition Particle (cpSRP)-targeting Components.
N. E. Lewis, N. J. Marty, K. M. Kathir, D. Rajalingam, A. D. Kight, A. Daily, T. K. S. Kumar, R. L. Henry, and R. L. Goforth (2010)
J. Biol. Chem. 285, 34220-34230
   Abstract »    Full Text »    PDF »
Lipid activation of the signal recognition particle receptor provides spatial coordination of protein targeting.
V. Q. Lam, D. Akopian, M. Rome, D. Henningsen, and S.-o. Shan (2010)
J. Cell Biol. 190, 623-635
   Abstract »    Full Text »    PDF »
The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence.
J. Trevino, N. Perez, and P. Sumby (2010)
Microbiology 156, 1342-1350
   Abstract »    Full Text »    PDF »
Transient tether between the SRP RNA and SRP receptor ensures efficient cargo delivery during cotranslational protein targeting.
K. Shen and S.-o. Shan (2010)
PNAS 107, 7698-7703
   Abstract »    Full Text »    PDF »
A Distinct Mechanism to Achieve Efficient Signal Recognition Particle (SRP)-SRP Receptor Interaction by the Chloroplast SRP Pathway.
P. Jaru-Ampornpan, T. X. Nguyen, and S.-o. Shan (2009)
Mol. Biol. Cell 20, 3965-3973
   Abstract »    Full Text »    PDF »
The Membrane-binding Motif of the Chloroplast Signal Recognition Particle Receptor (cpFtsY) Regulates GTPase Activity.
N. J. Marty, D. Rajalingam, A. D. Kight, N. E. Lewis, D. Fologea, T. K. S. Kumar, R. L. Henry, and R. L. Goforth (2009)
J. Biol. Chem. 284, 14891-14903
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882