Quantitative effect of scaffold abundance on signal propagation
Abstract Protein scaffolds bring together multiple components of a signalling pathway, thereby promoting signal propagation along a common physical ‘backbone’. Scaffolds play a prominent role in natural signalling pathways and provide a promising platform for synthetic circuits. To better understand...
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| Format: | Article |
| Language: | English |
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Springer Nature
2009-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2009.73 |
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| _version_ | 1850179311781281792 |
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| author | Stephen A Chapman Anand R Asthagiri |
| author_facet | Stephen A Chapman Anand R Asthagiri |
| author_sort | Stephen A Chapman |
| collection | DOAJ |
| description | Abstract Protein scaffolds bring together multiple components of a signalling pathway, thereby promoting signal propagation along a common physical ‘backbone’. Scaffolds play a prominent role in natural signalling pathways and provide a promising platform for synthetic circuits. To better understand how scaffolding quantitatively affects signal transmission, we conducted an in vivo sensitivity analysis of the yeast mating pathway to a broad range of perturbations in the abundance of the scaffold Ste5. Our measurements show that signal throughput exhibits a biphasic dependence on scaffold concentration and that altering the amount of scaffold binding partners reshapes this biphasic dependence. Unexpectedly, the wild‐type level of Ste5 is ∼10‐fold below the optimum needed to maximize signal throughput. This sub‐optimal configuration may be a tradeoff as increasing Ste5 expression promotes baseline activation of the mating pathway. Furthermore, operating at a sub‐optimal level of Ste5 may provide regulatory flexibility as tuning Ste5 expression up or down directly modulates the downstream phenotypic response. Our quantitative analysis reveals performance tradeoffs in scaffold‐based modules and defines engineering challenges for implementing molecular scaffolds in synthetic pathways. |
| format | Article |
| id | doaj-art-340f91c76c7f447b93b53250f4a31cea |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2009-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-340f91c76c7f447b93b53250f4a31cea2025-08-20T02:18:32ZengSpringer NatureMolecular Systems Biology1744-42922009-10-01511610.1038/msb.2009.73Quantitative effect of scaffold abundance on signal propagationStephen A Chapman0Anand R Asthagiri1Division of Chemistry and Chemical Engineering, California Institute of TechnologyDivision of Chemistry and Chemical Engineering, California Institute of TechnologyAbstract Protein scaffolds bring together multiple components of a signalling pathway, thereby promoting signal propagation along a common physical ‘backbone’. Scaffolds play a prominent role in natural signalling pathways and provide a promising platform for synthetic circuits. To better understand how scaffolding quantitatively affects signal transmission, we conducted an in vivo sensitivity analysis of the yeast mating pathway to a broad range of perturbations in the abundance of the scaffold Ste5. Our measurements show that signal throughput exhibits a biphasic dependence on scaffold concentration and that altering the amount of scaffold binding partners reshapes this biphasic dependence. Unexpectedly, the wild‐type level of Ste5 is ∼10‐fold below the optimum needed to maximize signal throughput. This sub‐optimal configuration may be a tradeoff as increasing Ste5 expression promotes baseline activation of the mating pathway. Furthermore, operating at a sub‐optimal level of Ste5 may provide regulatory flexibility as tuning Ste5 expression up or down directly modulates the downstream phenotypic response. Our quantitative analysis reveals performance tradeoffs in scaffold‐based modules and defines engineering challenges for implementing molecular scaffolds in synthetic pathways.https://doi.org/10.1038/msb.2009.73MAP kinase signallingpheromoneSaccharomyces cerevisiaesignal throughputSte5 scaffold |
| spellingShingle | Stephen A Chapman Anand R Asthagiri Quantitative effect of scaffold abundance on signal propagation Molecular Systems Biology MAP kinase signalling pheromone Saccharomyces cerevisiae signal throughput Ste5 scaffold |
| title | Quantitative effect of scaffold abundance on signal propagation |
| title_full | Quantitative effect of scaffold abundance on signal propagation |
| title_fullStr | Quantitative effect of scaffold abundance on signal propagation |
| title_full_unstemmed | Quantitative effect of scaffold abundance on signal propagation |
| title_short | Quantitative effect of scaffold abundance on signal propagation |
| title_sort | quantitative effect of scaffold abundance on signal propagation |
| topic | MAP kinase signalling pheromone Saccharomyces cerevisiae signal throughput Ste5 scaffold |
| url | https://doi.org/10.1038/msb.2009.73 |
| work_keys_str_mv | AT stephenachapman quantitativeeffectofscaffoldabundanceonsignalpropagation AT anandrasthagiri quantitativeeffectofscaffoldabundanceonsignalpropagation |