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Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity

The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7,...

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Autores principales: Trueman, Steven F., Mandon, Elisabet C., Gilmore, Reid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164448/
https://www.ncbi.nlm.nih.gov/pubmed/21737680
http://dx.doi.org/10.1091/mbc.E11-01-0070
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author Trueman, Steven F.
Mandon, Elisabet C.
Gilmore, Reid
author_facet Trueman, Steven F.
Mandon, Elisabet C.
Gilmore, Reid
author_sort Trueman, Steven F.
collection PubMed
description The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7, and TM8 in Sec61p) to expose the signal sequence–binding site. To gain mechanistic insight into lateral gate opening, mutations were introduced into a lumenal loop (L7) that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in both the posttranslational and cotranslational translocation pathways due to a kinetic delay in channel gating. The translocation defect caused by L7 mutations could be suppressed by the prl class of sec61 alleles, which reduce the fidelity of signal sequence recognition. The prl mutants are proposed to act by destabilizing the closed conformation of the translocation channel. Our results indicate that the equilibrium between the open and closed conformations of the protein translocation channel maintains a balance between translocation activity and signal sequence recognition fidelity.
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spelling pubmed-31644482011-11-16 Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity Trueman, Steven F. Mandon, Elisabet C. Gilmore, Reid Mol Biol Cell Articles The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7, and TM8 in Sec61p) to expose the signal sequence–binding site. To gain mechanistic insight into lateral gate opening, mutations were introduced into a lumenal loop (L7) that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in both the posttranslational and cotranslational translocation pathways due to a kinetic delay in channel gating. The translocation defect caused by L7 mutations could be suppressed by the prl class of sec61 alleles, which reduce the fidelity of signal sequence recognition. The prl mutants are proposed to act by destabilizing the closed conformation of the translocation channel. Our results indicate that the equilibrium between the open and closed conformations of the protein translocation channel maintains a balance between translocation activity and signal sequence recognition fidelity. The American Society for Cell Biology 2011-09-01 /pmc/articles/PMC3164448/ /pubmed/21737680 http://dx.doi.org/10.1091/mbc.E11-01-0070 Text en © 2011 Trueman 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 Biology.
spellingShingle Articles
Trueman, Steven F.
Mandon, Elisabet C.
Gilmore, Reid
Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
title Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
title_full Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
title_fullStr Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
title_full_unstemmed Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
title_short Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
title_sort translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164448/
https://www.ncbi.nlm.nih.gov/pubmed/21737680
http://dx.doi.org/10.1091/mbc.E11-01-0070
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