Thresholds, long delays and stability from generalized allosteric effect in protein networks

Roberto Chignola, Chiara Dalla Pellegrina, Alessio Del Fabbro and Edoardo Milotti

Physica A: Statistical Mechanics and its Applications, 2006, vol. 371, issue 2, 463-472

Abstract: Post-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation are well known to play a pivotal role in the intracellular transduction of activation and death signals. A protein can have multiple sites where chemical groups can reversibly attach in processes such as phosphorylation or nitrosylation. A microscopic description of these processes must take into account the intrinsic probabilistic nature of the underlying reactions. We apply combinatorial considerations to standard enzyme kinetics and in this way we extend to the dynamic regime a simplified version of the traditional models on the allosteric regulation of protein functions. We link a generic modification chain to a downstream Michaelis–Menten enzymatic reaction and we demonstrate numerically that this accounts both for thresholds and long time delays in the conversion of the substrate by the enzyme. The proposed mechanism is stable and robust and the higher the number of modification sites, the greater the stability. We show that a high number of modification sites converts a fast reaction into a slow process, and the slowing down depends on the number of sites and may span many orders of magnitude; in this way multisite modification of proteins stands out as a general mechanism that allows the transfer of information from the very short time scales of enzyme reactions (milliseconds) to the long time scale of cell response (hours).

Keywords: Multisite phosphorylation; Nitrosylation; Threshold effect; Biochemical model; Network dynamics (search for similar items in EconPapers)
Date: 2006
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Persistent link: https://EconPapers.repec.org/RePEc:eee:phsmap:v:371:y:2006:i:2:p:463-472

DOI: 10.1016/j.physa.2006.03.044

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