Symmetry breaking meets multisite modification

  1. Vaidhiswaran Ramesh
  2. J Krishnan  Is a corresponding author
  1. Imperial College London, United Kingdom

Abstract

Multisite modification is a basic way of conferring functionality to proteins, and a key component of post-translational modification networks. Additional interest in multisite modification stems from its capability of acting as complex information processors. In this paper we connect two seemingly disparate themes: symmetry and multisite modification. We examine different classes of random modification networks of substrates involving separate or common enzymes. We demonstrate that under different instances of symmetry of the modification network (invoked explicitly or implicitly and discussed in the literature), the biochemistry of multisite modification can lead to the symmetry being broken. This is shown computationally and consolidated analytically, revealing parameter regions where this can (and in fact does) happen, and characteristics of the symmetry broken state. We discuss the relevance of these results in situations where exact symmetry is not present. Overall, through our study we show how symmetry breaking (i) can confer new capabilities to protein networks, including concentration robustness of different combinations of species (in conjunction with multiple steady states) (ii) could have been the basis for ordering of multisite modification, which is widely observed in cells (iii) can significantly impact information processing in multisite modification and in cell signalling networks/pathways where multisite modification is present (iv) can be a fruitful new angle for engineering in synthetic biology and chemistry. All in all, the emerging conceptual synthesis provides a new vantage point for the elucidation and the engineering of molecular systems at the junction of chemical and biological systems.

Data availability

All data generated or analyzed during this study are included in this manuscript and supporting files. Relevant source code is also provided

Article and author information

Author details

  1. Vaidhiswaran Ramesh

    Department of Chemical Engineerng, Centre for Process Systems Engineering, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. J Krishnan

    Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, London, United Kingdom
    For correspondence
    j.krishnan@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6196-2033

Funding

The authors declare that no external funding was received for this work

Copyright

© 2021, Ramesh & Krishnan

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 886
    views
  • 156
    downloads
  • 3
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Vaidhiswaran Ramesh
  2. J Krishnan
(2021)
Symmetry breaking meets multisite modification
eLife 10:e65358.
https://doi.org/10.7554/eLife.65358

Share this article

https://doi.org/10.7554/eLife.65358

Further reading

    1. Physics of Living Systems
    Tommaso Amico, Samuel Toluwanimi Dada ... Amos Maritan
    Research Article

    Many proteins have been recently shown to undergo a process of phase separation that leads to the formation of biomolecular condensates. Intriguingly, it has been observed that some of these proteins form dense droplets of sizeable dimensions already below the critical concentration, which is the concentration at which phase separation occurs. To understand this phenomenon, which is not readily compatible with classical nucleation theory, we investigated the properties of the droplet size distributions as a function of protein concentration. We found that these distributions can be described by a scale-invariant log-normal function with an average that increases progressively as the concentration approaches the critical concentration from below. The results of this scaling analysis suggest the existence of a universal behaviour independent of the sequences and structures of the proteins undergoing phase separation. While we refrain from proposing a theoretical model here, we suggest that any model of protein phase separation should predict the scaling exponents that we reported here from the fitting of experimental measurements of droplet size distributions. Furthermore, based on these observations, we show that it is possible to use the scale invariance to estimate the critical concentration for protein phase separation.

    1. Computational and Systems Biology
    2. Physics of Living Systems
    Ju Kang, Shijie Zhang ... Xin Wang
    Research Article

    Explaining biodiversity is a fundamental issue in ecology. A long-standing puzzle lies in the paradox of the plankton: many species of plankton feeding on a limited variety of resources coexist, apparently flouting the competitive exclusion principle (CEP), which holds that the number of predator (consumer) species cannot exceed that of the resources at a steady state. Here, we present a mechanistic model and demonstrate that intraspecific interference among the consumers enables a plethora of consumer species to coexist at constant population densities with only one or a handful of resource species. This facilitated biodiversity is resistant to stochasticity, either with the stochastic simulation algorithm or individual-based modeling. Our model naturally explains the classical experiments that invalidate the CEP, quantitatively illustrates the universal S-shaped pattern of the rank-abundance curves across a wide range of ecological communities, and can be broadly used to resolve the mystery of biodiversity in many natural ecosystems.