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Published June 9, 2014 | Published + Supplemental Material
Journal Article Open

Regulation of cargo recognition, commitment, and unloading drives cotranslational protein targeting


Efficient and accurate protein localization is essential to cells and requires protein-targeting machineries to both effectively capture the cargo in the cytosol and productively unload the cargo at the membrane. To understand how these challenges are met, we followed the interaction of translating ribosomes during their targeting by the signal recognition particle (SRP) using a site-specific fluorescent probe in the nascent protein. We show that initial recruitment of SRP receptor (SR) selectively enhances the affinity of SRP for correct cargos, thus committing SRP-dependent substrates to the pathway. Real-time measurement of cargo transfer from the targeting to translocation machinery revealed multiple factors that drive this event, including GTPase rearrangement in the SRP–SR complex, stepwise displacement of SRP from the ribosome and signal sequence by SecYEG, and elongation of the nascent polypeptide. Our results elucidate how active and sequential regulation of the SRP–cargo interaction drives efficient and faithful protein targeting.

Additional Information

© 2014 Saraogi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). Submitted: 7 November 2013; Accepted: 1 May 2014; Published June 9, 2014. We thank Tom Miller and Connie Wang for discussions and members of the Shan group for comments on the manuscript. This work was supported by National Institutes of Health grant GM078024 to S.-o. Shan. S.-o. Shan was supported by the Henry Dreyfus teacher-scholar award and the Packard and Lucile Fellowship in science and engineering. This project is funded in part by the Gordon and Betty Moore Foundation through grant GBMF2939 to S.-o. Shan. The authors declare no competing financial interests.

Attached Files

Published - J_Cell_Biol-2014-Saraogi-693-706.pdf

Supplemental Material - JCB_201311028_sm.pdf


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