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Phosphorelays provide tunable signal processing capabilities for the cell
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Kothamachu, Varun B., Feliu, Elisenda, Wiuf, Carsten, Cardelli, Luca and Soyer, Orkun S. (2013) Phosphorelays provide tunable signal processing capabilities for the cell. PLoS Computational Biology, Volume 9 (Number 11). Article number e1003322. doi:10.1371/journal.pcbi.1003322
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WRAP_Soyer_journal.pcbi.1003322.pdf - Published Version Available under License Creative Commons Attribution. Download (586Kb) | Preview |
Official URL: http://dx.doi.org/10.1371/journal.pcbi.1003322
Abstract
Achieving a complete understanding of cellular signal transduction requires deciphering the relation between structural and biochemical features of a signaling system and the shape of the signal-response relationship it embeds. Using explicit analytical expressions and numerical simulations, we present here this relation for four-layered phosphorelays, which are signaling systems that are ubiquitous in prokaryotes and also found in lower eukaryotes and plants. We derive an analytical expression that relates the shape of the signal-response relationship in a relay to the kinetic rates of forward, reverse phosphorylation and hydrolysis reactions. This reveals a set of mathematical conditions which, when satisfied, dictate the shape of the signal-response relationship. We find that a specific topology also observed in nature can satisfy these conditions in such a way to allow plasticity among hyperbolic and sigmoidal signal-response relationships. Particularly, the shape of the signal-response relationship of this relay topology can be tuned by altering kinetic rates and total protein levels at different parts of the relay. These findings provide an important step towards predicting response dynamics of phosphorelays, and the nature of subsequent physiological responses that they mediate, solely from topological features and few composite measurements; measuring the ratio of reverse and forward phosphorylation rate constants could be sufficient to determine the shape of the signal-response relationship the relay exhibits. Furthermore, they highlight the potential ways in which selective pressures on signal processing could have played a role in the evolution of the observed structural and biochemical characteristic in phosphorelays.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Cellular signal transduction, Phosphorylation , Signal processing | ||||
| Journal or Publication Title: | PLoS Computational Biology | ||||
| Publisher: | Public Library of Science | ||||
| ISSN: | 1553-7358 | ||||
| Official Date: | 7 November 2013 | ||||
| Dates: |
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| Volume: | Volume 9 | ||||
| Number: | Number 11 | ||||
| Page Range: | Article number e1003322 | ||||
| DOI: | 10.1371/journal.pcbi.1003322 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Comissionat per Universitats i Recerca de la Generalitat de Catalunya (CURGC), Spain. Cortes Generales, Carlsbergfondet (Copenhagen, Denmark) [Carlsberg foundation], Lundbeck Foundation, Engineering and Physical Sciences Research Council (EPSRC), Microsoft Research | ||||
| Grant number: | MTM2009-14163-C02-01 |
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