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Fingerloop activates cargo delivery and unloading during cotranslational protein targeting

Ariosa, Aileen R. and Duncan, Stacy S. and Saraogi, Ishu and Lu, Xiaodong and Brown, April and Phillips, Gregory J. and Shan, Shu-ou (2013) Fingerloop activates cargo delivery and unloading during cotranslational protein targeting. Molecular Biology of the Cell, 24 (2). pp. 63-73. ISSN 1059-1524. PMCID PMC3541965. doi:10.1091/mbc.E12-06-0434. https://resolver.caltech.edu/CaltechAUTHORS:20130722-092857106

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Abstract

During cotranslational protein targeting by the signal recognition particle (SRP), information about signal sequence binding in the SRP's M domain must be effectively communicated to its GTPase domain to turn on its interaction with the SRP receptor (SR) and thus deliver the cargo proteins to the membrane. A universally conserved “fingerloop” lines the signal sequence–binding groove of SRP; the precise role of this fingerloop in protein targeting has remained elusive. In this study, we show that the fingerloop plays important roles in SRP function by helping to induce the SRP into a more active conformation that facilitates multiple steps in the pathway, including efficient recruitment of SR, GTPase activation in the SRP•SR complex, and most significantly, the unloading of cargo onto the target membrane. On the basis of these results and recent structural work, we propose that the fingerloop is the first structural element to detect signal sequence binding; this information is relayed to the linker connecting the SRP's M and G domains and thus activates the SRP and SR for carrying out downstream steps in the pathway.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1091/mbc.E12-06-0434DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541965/PubMed CentralArticle
ORCID:
AuthorORCID
Brown, April0000-0003-2631-3905
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2013 Ariosa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). Received: Jun 12, 2012; Revised: Oct 25, 2012; Accepted: Nov 1, 2012. We thank members of the Shan group for helpful comments on the manuscript. This work was supported by National Institutes of Health (NIH) grant GM078024, the Beckman Young Investigator Award, the David and Lucile Packard Fellowship in Science and Engineering, and the Henry Dreyfus Teacher-Scholar Award to S.-O.S. G.J.P. was supported by NIH grant R01 GM069628. A.R.A. was supported by NIH/NRSA training grant 5T32GM07616 and by the Betty and Gordon Moore Foundation.
Funders:
Funding AgencyGrant Number
NIHGM078024
Arnold and Mabel Beckman FoundationUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Camille and Henry Dreyfus FoundationUNSPECIFIED
NIHR01 GM069628
NIH Predoctoral Fellowship5T32GM07616
Gordon and Betty Moore FoundationUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC3541965
DOI:10.1091/mbc.E12-06-0434
Record Number:CaltechAUTHORS:20130722-092857106
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130722-092857106
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39488
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:22 Jul 2013 17:05
Last Modified:09 Nov 2021 23:45

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