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Fingerloop activates cargo delivery and unloading during cotranslational protein targeting

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 t...

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Autores principales: Ariosa, Aileen R., Duncan, Stacy S., Saraogi, Ishu, Lu, Xiaodong, Brown, April, Phillips, Gregory J., Shan, Shu-Ou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541965/
https://www.ncbi.nlm.nih.gov/pubmed/23135999
http://dx.doi.org/10.1091/mbc.E12-06-0434
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author Ariosa, Aileen R.
Duncan, Stacy S.
Saraogi, Ishu
Lu, Xiaodong
Brown, April
Phillips, Gregory J.
Shan, Shu-Ou
author_facet Ariosa, Aileen R.
Duncan, Stacy S.
Saraogi, Ishu
Lu, Xiaodong
Brown, April
Phillips, Gregory J.
Shan, Shu-Ou
author_sort Ariosa, Aileen R.
collection PubMed
description 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.
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spelling pubmed-35419652013-03-30 Fingerloop activates cargo delivery and unloading during cotranslational protein targeting Ariosa, Aileen R. Duncan, Stacy S. Saraogi, Ishu Lu, Xiaodong Brown, April Phillips, Gregory J. Shan, Shu-Ou Mol Biol Cell Articles 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. The American Society for Cell Biology 2013-01-15 /pmc/articles/PMC3541965/ /pubmed/23135999 http://dx.doi.org/10.1091/mbc.E12-06-0434 Text en © 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). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Ariosa, Aileen R.
Duncan, Stacy S.
Saraogi, Ishu
Lu, Xiaodong
Brown, April
Phillips, Gregory J.
Shan, Shu-Ou
Fingerloop activates cargo delivery and unloading during cotranslational protein targeting
title Fingerloop activates cargo delivery and unloading during cotranslational protein targeting
title_full Fingerloop activates cargo delivery and unloading during cotranslational protein targeting
title_fullStr Fingerloop activates cargo delivery and unloading during cotranslational protein targeting
title_full_unstemmed Fingerloop activates cargo delivery and unloading during cotranslational protein targeting
title_short Fingerloop activates cargo delivery and unloading during cotranslational protein targeting
title_sort fingerloop activates cargo delivery and unloading during cotranslational protein targeting
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541965/
https://www.ncbi.nlm.nih.gov/pubmed/23135999
http://dx.doi.org/10.1091/mbc.E12-06-0434
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