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Macromolecular assemblies such as protein complexes and protein/RNA condensates are involved in most fundamental cellular processes. The arrangement of subunits within these nano-assemblies is critical for their biological function and is determined by the topology of physical contacts within and between the subunits forming the complex. Describing the spatial arrangement of these interactions is of central importance to understand their functional and stability consequences. In this concept article, we propose a circuit topology-based formalism to define the topology of a complex consisting of linear polymeric chains with inter- and intrachain interactions. We apply our method to a system of model polymer chains as well as protein assemblies. We show that circuit topology can categorize different forms of chain assemblies. Our multi-chain circuit topology should aid analysis and predictions of mechanistic and evolutionary principles in the design of macromolecular assemblies.


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A topology framework for macromolecular complexes and condensates

Show Author's information Maziar Heidari1Duane Moes1Otto Schullian1,2Barbara Scalvini1Alireza Mashaghi1,3( )
Medical Systems Biophysics and Bioengineering, Leiden Academic Centre for Drug Research, Faculty of Science, Leiden University, Leiden 2333CC, the Netherlands
Fachbereich Physik, Freie Universität Berlin, Arnimallee 14, Berlin 14195, Germany
Harvard Medical School, Harvard University, 25 Shattuck St, Boston MA 02115, USA

Abstract

Macromolecular assemblies such as protein complexes and protein/RNA condensates are involved in most fundamental cellular processes. The arrangement of subunits within these nano-assemblies is critical for their biological function and is determined by the topology of physical contacts within and between the subunits forming the complex. Describing the spatial arrangement of these interactions is of central importance to understand their functional and stability consequences. In this concept article, we propose a circuit topology-based formalism to define the topology of a complex consisting of linear polymeric chains with inter- and intrachain interactions. We apply our method to a system of model polymer chains as well as protein assemblies. We show that circuit topology can categorize different forms of chain assemblies. Our multi-chain circuit topology should aid analysis and predictions of mechanistic and evolutionary principles in the design of macromolecular assemblies.

Keywords: topology, folding, macromolecular complex, protein evolution

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Publication history

Received: 02 February 2022
Revised: 21 March 2022
Accepted: 22 March 2022
Published: 19 May 2022
Issue date: November 2022

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© The Author(s) 2022

Acknowledgements

Acknowledgements

The authors thank Martin Karplus (Harvard University), Arjen Jakobi (Delft University of Technology), and Alexandre Dawid (University Grenoble Alpes) for helpful discussions and critical reading of the manuscript.

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