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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Main Authors:	Kothamachu, Varun B., Feliu, Elisenda, Wiuf, Carsten, Cardelli, Luca, Soyer, Orkun S.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820541/

id	pubmed-3820541
recordtype	oai_dc
spelling	pubmed-38205412013-11-15 Phosphorelays Provide Tunable Signal Processing Capabilities for the Cell Kothamachu, Varun B. Feliu, Elisenda Wiuf, Carsten Cardelli, Luca Soyer, Orkun S. Research Article 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. Public Library of Science 2013-11-07 /pmc/articles/PMC3820541/ /pubmed/24244132 http://dx.doi.org/10.1371/journal.pcbi.1003322 Text en © 2013 Kothamachu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kothamachu, Varun B. Feliu, Elisenda Wiuf, Carsten Cardelli, Luca Soyer, Orkun S.
spellingShingle	Kothamachu, Varun B. Feliu, Elisenda Wiuf, Carsten Cardelli, Luca Soyer, Orkun S. Phosphorelays Provide Tunable Signal Processing Capabilities for the Cell
author_facet	Kothamachu, Varun B. Feliu, Elisenda Wiuf, Carsten Cardelli, Luca Soyer, Orkun S.
author_sort	Kothamachu, Varun B.
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
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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820541/
_version_	1612024358516031488

Phosphorelays Provide Tunable Signal Processing Capabilities for the Cell

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