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Demonstration of a Multistep Mechanism for Assembly of the SRP·SRP Receptor Complex: Implications for the Catalytic Role of SRP RNA

Zhang, Xin and Kung, Simon and Shan, Shu-ou (2008) Demonstration of a Multistep Mechanism for Assembly of the SRP·SRP Receptor Complex: Implications for the Catalytic Role of SRP RNA. Journal of Molecular Biology, 381 (3). pp. 581-593. ISSN 0022-2836. PMCID PMC2630804. doi:10.1016/j.jmb.2008.05.049. https://resolver.caltech.edu/CaltechAUTHORS:20120726-073902314

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Abstract

Two GTPases in the signal recognition particle (SRP) and its receptor (SR) control the delivery of newly synthesized proteins to the endoplasmic reticulum or plasma membrane. During the protein targeting reaction, the 4.5S SRP RNA accelerates the association between the two GTPases by 400-fold. Using fluorescence resonance energy transfer, we demonstrate here that formation of a stable SRP·SR complex involves two distinct steps: a fast initial association between SRP and SR to form a GTP-independent early complex and then a GTP-dependent conformational rearrangement to form the stable final complex. We also found that the 4.5S SRP RNA significantly stabilizes the early GTP-independent intermediate. Furthermore, mutational analyses show that there is a strong correlation between the ability of the mutant SRP RNAs to stabilize the early intermediate and their ability to accelerate SRP·SR complex formation. We propose that the SRP RNA, by stabilizing the early intermediate, can give this transient intermediate a longer life time and therefore a higher probability to rearrange to the stable final complex. This provides a coherent model that explains how the 4.5S RNA exerts its catalytic role in SRP·SR complex assembly.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jmb.2008.05.049 DOIArticle
http://www.sciencedirect.com/science/article/pii/S002228360800630XPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630804/PubMed CentralArticle
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2008 Elsevier Ltd. Received 16 April 2008. Revised 20 May 2008. Accepted 20 May 2008. Available online 29 May 2008. Edited by J. Doudna. This work was supported by the National Institutes of Health through grant GM078024 to S.S. S.S. was supported by a Burroughs Wellcome Fund Career Award, the Henry and Camille Dreyfus Foundation, a Beckman Young Investigator Award, and a Packard and Lucile Award in Science and Engineering. X.Z. was supported by a fellowship from the Ulric B. and Evelyn L. Bray Endowment Fund. We thank members of the Shan laboratory for their comments on the manuscript.
Funders:
Funding AgencyGrant Number
NIHGM078024
Burroughs Wellcome FundUNSPECIFIED
Camille and Henry Dreyfus FoundationUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Ulric B. and Evelyn L. Bray Endowment FundUNSPECIFIED
Subject Keywords:signal recognition particle; protein targeting and translocation; GTPases; SRP RNA; fluorescence resonance energy transfer
Issue or Number:3
PubMed Central ID:PMC2630804
DOI:10.1016/j.jmb.2008.05.049
Record Number:CaltechAUTHORS:20120726-073902314
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120726-073902314
Official Citation:Xin Zhang, Simon Kung, Shu-ou Shan, Demonstration of a Multistep Mechanism for Assembly of the SRP·SRP Receptor Complex: Implications for the Catalytic Role of SRP RNA, Journal of Molecular Biology, Volume 381, Issue 3, 5 September 2008, Pages 581-593, ISSN 0022-2836, 10.1016/j.jmb.2008.05.049.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:32731
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:26 Jul 2012 23:15
Last Modified:09 Nov 2021 21:29

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