Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published December 20, 2013 | Supplemental Material + Published
Journal Article Open

Molecular Mechanism of GTPase Activation at the Signal Recognition Particle (SRP) RNA Distal End


The signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates the co-translational targeting of proteins to the correct cellular membrane. During the targeting reaction, two functional ends in the SRP RNA mediate distinct functions. Whereas the RNA tetraloop facilitates initial assembly of two GTPases between the SRP and SRP receptor, this GTPase complex subsequently relocalizes ∼100 Å to the 5′,3′-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover. Here we combined biochemical, single molecule, and NMR studies to investigate the molecular mechanism of this large scale conformational change. We show that two independent sites contribute to the interaction of the GTPase complex with the SRP RNA distal end. Loop E plays a crucial role in the precise positioning of the GTPase complex on these two sites by inducing a defined bend in the RNA helix and thus generating a preorganized recognition surface. GTPase docking can be uncoupled from its subsequent activation, which is mediated by conserved bases in the next internal loop. These results, combined with recent structural work, elucidate how the SRP RNA induces GTPase relocalization and activation at the end of the protein targeting reaction.

Additional Information

© 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Received August 24, 2013. Revision received October 9, 2013. First Published on October 22, 2013. This work was supported, in whole or in part, by National Institutes of Health Grants GM078024 (to S.-o.S.) and GM048123 (to J. F.) and a National Institutes of Health instrument supplement to Grant GM45162 (to D. C. Rees). This work was also supported by Caltech Matching Fund 350270 for the single molecule instruments, the David and Lucile Packard Fellowship in Science and Engineering (to S.-o.S.), and a Henry Dreyfus teacher-scholar award (to S.-o.S.).

Attached Files

Published - J._Biol._Chem.-2013-Shen-36385-97.pdf

Supplemental Material - jbc.M113.513614-1.docx


Files (5.6 MB)
Name Size Download all
5.5 MB Preview Download
83.2 kB Download

Additional details

August 22, 2023
October 25, 2023