Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch

Abstract Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires el...

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Autores principales:	Allen K. Kim, Helen D. Wu, Takanari Inoue
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9cb8eb4962a94741883e9e8e641af37a
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spelling	oai:doaj.org-article:9cb8eb4962a94741883e9e8e641af37a2021-12-02T16:28:50ZSynthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch10.1038/s41598-021-95840-82045-2322https://doaj.org/article/9cb8eb4962a94741883e9e8e641af37a2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95840-8https://doaj.org/toc/2045-2322Abstract Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires elaborate coordination of sensing and actuation mechanisms built into a single molecule. Here, we rationally designed a molecular switch that changes its subcellular localization in response to an intended stimulus such as an activator of protein kinase A (PKA). By arranging the sequence for Kemptide in tandem, we designed a farnesylated peptide whose localization can dramatically change upon phosphorylation by PKA. After testing a different valence number of Kemptide as well as modulating the linker sequence connecting them, we identified an efficient peptide switch that exhibited dynamic translocation between plasma membranes and internal endomembranes in a PKA activity dependent manner. Due to the modular design and small size, our PKA switch can have versatile utility in future studies as a platform for visualizing and perturbing signal transduction pathways, as well as for performing synthetic operations in cells.Allen K. KimHelen D. WuTakanari InoueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allen K. Kim Helen D. Wu Takanari Inoue Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
description	Abstract Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires elaborate coordination of sensing and actuation mechanisms built into a single molecule. Here, we rationally designed a molecular switch that changes its subcellular localization in response to an intended stimulus such as an activator of protein kinase A (PKA). By arranging the sequence for Kemptide in tandem, we designed a farnesylated peptide whose localization can dramatically change upon phosphorylation by PKA. After testing a different valence number of Kemptide as well as modulating the linker sequence connecting them, we identified an efficient peptide switch that exhibited dynamic translocation between plasma membranes and internal endomembranes in a PKA activity dependent manner. Due to the modular design and small size, our PKA switch can have versatile utility in future studies as a platform for visualizing and perturbing signal transduction pathways, as well as for performing synthetic operations in cells.
format	article
author	Allen K. Kim Helen D. Wu Takanari Inoue
author_facet	Allen K. Kim Helen D. Wu Takanari Inoue
author_sort	Allen K. Kim
title	Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
title_short	Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
title_full	Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
title_fullStr	Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
title_full_unstemmed	Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
title_sort	synthetic design of farnesyl-electrostatic peptides for development of a protein kinase a membrane translocation switch
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9cb8eb4962a94741883e9e8e641af37a
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Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch

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