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Conformational changes in the GTPase modules of the signal reception particle and its receptor drive initiation of protein translocation

Shan, Shu-ou and Chandrasekar, Sowmya and Walter, Peter (2007) Conformational changes in the GTPase modules of the signal reception particle and its receptor drive initiation of protein translocation. Journal of Cell Biology, 178 (4). pp. 611-620. ISSN 0021-9525. PMCID PMC2064468. https://resolver.caltech.edu/CaltechAUTHORS:SHAjcb07

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Abstract

During cotranslational protein targeting, two guanosine triphosphatase (GTPase) in the signal recognition particle (SRP) and its receptor (SR) form a unique complex in which hydrolyses of both guanosine triphosphates (GTP) are activated in a shared active site. It was thought that GTP hydrolysis drives the recycling of SRP and SR, but is not crucial for protein targeting. Here, we examined the translocation efficiency of mutant GTPases that block the interaction between SRP and SR at specific stages. Surprisingly, mutants that allow SRP–SR complex assembly but block GTPase activation severely compromise protein translocation. These mutations map to the highly conserved insertion box domain loops that rearrange upon complex formation to form multiple catalytic interactions with the two GTPs. Thus, although GTP hydrolysis is not required, the molecular rearrangements that lead to GTPase activation are essential for protein targeting. Most importantly, our results show that an elaborate rearrangement within the SRP–SR GTPase complex is required to drive the unloading and initiate translocation of cargo proteins.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064468/PubMed CentralArticle
https://doi.org/10.1083/jcb.200702018DOIUNSPECIFIED
https://doi.org/10.1083/jcb.200702018DOIUNSPECIFIED
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© The Rockefeller University Press, 2007. Submitted: 5 February 2007. Accepted: 1 July 2007. Published online 6 August 2007. We thank Ted Powers for help in reconstituting the heterologous protein targeting reaction. This work was supported by National Institutes of Health grant GM 32384 to P. Walter and career awards from the Burroughs Wellcome Fund and the Camille and Henry Dreyfus Foundation to S. Shan. P. Walter is an investigator at the Howard Hughes Medical Institute. Fig. S1 shows that the targeting and translocation of pPL occurs on a faster time scale than completion of protein synthesis. Fig. S2 shows that FtsY(47–497) is reduced by about half in translocation of pPL compared with full-length FtsY. Fig. S3 and Tables S1–S7 show additional data for repetitions of the experiments shown in Figs. 2–5. Online supplemental material is available at http://www.jcb.org/cgi/content/full/jcb.200702018/DC1.
Issue or Number:4
PubMed Central ID:PMC2064468
Record Number:CaltechAUTHORS:SHAjcb07
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:SHAjcb07
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8529
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:17 Aug 2007
Last Modified:02 Oct 2019 23:51

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