Phosphorelays provide tunable signal processing capabilities for the cell.

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 pres...

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Autores principales:	Varun B Kothamachu, Elisenda Feliu, Carsten Wiuf, Luca Cardelli, Orkun S Soyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e8cf14fe23284a9896dd98f2576e519a
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spelling	oai:doaj.org-article:e8cf14fe23284a9896dd98f2576e519a2021-11-18T05:53:25ZPhosphorelays provide tunable signal processing capabilities for the cell.1553-734X1553-735810.1371/journal.pcbi.1003322https://doaj.org/article/e8cf14fe23284a9896dd98f2576e519a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244132/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Achieving 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.Varun B KothamachuElisenda FeliuCarsten WiufLuca CardelliOrkun S SoyerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 11, p e1003322 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Varun B Kothamachu Elisenda Feliu Carsten Wiuf Luca Cardelli Orkun S Soyer Phosphorelays provide tunable signal processing capabilities for the cell.
description	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.
format	article
author	Varun B Kothamachu Elisenda Feliu Carsten Wiuf Luca Cardelli Orkun S Soyer
author_facet	Varun B Kothamachu Elisenda Feliu Carsten Wiuf Luca Cardelli Orkun S Soyer
author_sort	Varun B Kothamachu
title	Phosphorelays provide tunable signal processing capabilities for the cell.
title_short	Phosphorelays provide tunable signal processing capabilities for the cell.
title_full	Phosphorelays provide tunable signal processing capabilities for the cell.
title_fullStr	Phosphorelays provide tunable signal processing capabilities for the cell.
title_full_unstemmed	Phosphorelays provide tunable signal processing capabilities for the cell.
title_sort	phosphorelays provide tunable signal processing capabilities for the cell.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e8cf14fe23284a9896dd98f2576e519a
work_keys_str_mv	AT varunbkothamachu phosphorelaysprovidetunablesignalprocessingcapabilitiesforthecell AT elisendafeliu phosphorelaysprovidetunablesignalprocessingcapabilitiesforthecell AT carstenwiuf phosphorelaysprovidetunablesignalprocessingcapabilitiesforthecell AT lucacardelli phosphorelaysprovidetunablesignalprocessingcapabilitiesforthecell AT orkunssoyer phosphorelaysprovidetunablesignalprocessingcapabilitiesforthecell
_version_	1718424700624830464

Phosphorelays provide tunable signal processing capabilities for the cell.

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