Symmetry breaking meets multisite modification

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


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
    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


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

Reviewing Editor

  1. Olivier Rivoire, College de France, France

Version history

  1. Received: December 1, 2020
  2. Accepted: May 20, 2021
  3. Accepted Manuscript published: May 21, 2021 (version 1)
  4. Version of Record published: September 14, 2021 (version 2)


© 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.


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  1. Vaidhiswaran Ramesh
  2. J Krishnan
Symmetry breaking meets multisite modification
eLife 10:e65358.

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