Movatterモバイル変換


[0]ホーム

URL:


Skip to main content
Springer Nature Link
Log in

A topology framework for macromolecular complexes and condensates

You have full access to thisopen access article

Nano Research Aims and scope

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.

Article PDF

Similar content being viewed by others

Use our pre-submission checklist

Avoid common mistakes on your manuscript.

References

  1. Alberti, S.; Hyman, A. A. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing.Nat. Rev. Mol. Cell Biol.2021,22, 196–213.

    Article CAS PubMed  Google Scholar 

  2. Marx, V. Cell biology befriends soft matter physics.Nat. Methods2020,17, 567–570.

    Article CAS PubMed  Google Scholar 

  3. Virnau, P.; Mirny, L. A.; Kardar, M. Intricate knots in proteins: Function and evolution.PLoS Comput. Biol.2006,2 e122.

    Article PubMed  Google Scholar 

  4. Mashaghi, A.; van Wijk, R. J.; Tans, S. J. Circuit topology of proteins and nucleic acids.Structure2014,22, 1227–1237.

    Article CAS PubMed  Google Scholar 

  5. Golovnev, A.; Mashaghi, A. Generalized circuit topology of folded linear chains.iScience2020,23, 101492.

    Article CAS PubMed  Google Scholar 

  6. Mugler, A.; Tans, S. J.; Mashaghi, A. Circuit topology of self-interacting chains: Implications for folding and unfolding dynamics.Phys. Chem. Chem. Phys.2014,16, 22537–22544.

    Article CAS PubMed  Google Scholar 

  7. Scalvini, B.; Sheikhhassani, V.; Mashaghi, A. Topological principles of protein folding.Phys. Chem. Chem. Phys.2021,23, 21316–21328.

    Article CAS PubMed  Google Scholar 

  8. Heidari, M.; Schiessel, H.; Mashaghi, A. Circuit topology analysis of polymer folding reactions.ACS Cent. Sci.2020,6, 839–847.

    Article CAS PubMed  Google Scholar 

  9. Schullian, O.; Woodard, J.; Tirandaz, A.; Mashaghi, A. A circuit topology approach to categorizing changes in biomolecular structure.Front. Phys.2020,8, 5.

    Article  Google Scholar 

  10. Levy, E. D.; Pereira-Leal, J. B.; Chothia, C.; Teichmann, S. A. 3D complex: A structural classification of protein complexes.PLoS Comput. Biol.2006,2, e155.

    Article PubMed PubMed Central  Google Scholar 

  11. Ozawa, Y.; Saito, R.; Fujimori, S.; Kashima, H.; Ishizaka, M.; Yanagawa, H.; Miyamoto-Sato, E.; Tomita, M. Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions.BMC Bioinformatics2010,11, 350.

    Article PubMed PubMed Central  Google Scholar 

  12. Mashaghi, A. R.; Ramezanpour, A.; Karimipour, V. Investigation of a protein complex network.Eur. Phys. J. B2004,41, 113–121.

    Article CAS  Google Scholar 

  13. Gutmanas, A.; Alhroub, Y.; Battle, G. M.; Berrisford, J. M.; Bochet, E.; Conroy, M. J.; Dana, J. M.; Montecelo, M. A. F.; van Ginkel, G. et al. PDBe: Protein data bank in Europe.Nucleic Acids Res.2014,42, D285–D291.

    Article CAS PubMed  Google Scholar 

  14. Kopp, J.; Schwede, T. The SWISS-MODEL Repository: New features and functionalities.Nucleic Acids Res.2006,34, D315–D318.

    Article CAS PubMed  Google Scholar 

  15. Bruce, J. E.In vivo protein complex topologies: Sights through a cross-linking lens.Proteomics2012,12, 1565–1575.

    Article CAS PubMed PubMed Central  Google Scholar 

  16. Politis, A.; Schmidt, C.; Tjioe, E.; Sandercock, A. M.; Lasker, K.; Gordiyenko, Y.; Russel, D.; Sali, A.; Robinson, C. V. Topological models of heteromeric protein assemblies from mass spectrometry: Application to the yeast eIF3:eIF5 complex.Chem. Biol.2015,22, 117–128.

    Article CAS PubMed PubMed Central  Google Scholar 

  17. Zheng, C. X.; Yang, L.; Hoopmann, M. R.; Eng, J. K.; Tang, X. T.; Weisbrod, C. R.; Bruce, J. E. Cross-linking measurements ofin vivo protein complex topologies.Mol. Cell. Proteomics2011,10, M110.006841.

    Article PubMed PubMed Central  Google Scholar 

  18. Kremer, K.; Grest, G. S. Dynamics of entangled linear polymer melts: A molecular-dynamics simulation.J. Chem. Phys.1990,92, 5057–5086.

    Article CAS  Google Scholar 

  19. Plimpton, S. Fast parallel algorithms for short-range molecular dynamics.J. Comput. Phys.1995,117, 1–19.

    Article CAS  Google Scholar 

  20. Alexander-Katz, A.; Schneider, M. F.; Schneider, S. W.; Wixforth, A.; Netz, R. R. Shear-flow-induced unfolding of polymeric globules.Phys. Rev. Lett.2006,97, 138101.

    Article CAS PubMed  Google Scholar 

  21. Heidari, M.; Satarifard, V.; Mashaghi, A. Mapping a single-molecule folding process onto a topological space.Phys. Chem. Chem. Phys.2019,21, 20338–20345.

    Article CAS PubMed  Google Scholar 

  22. de Gennes, P. G.Scaling Concepts in Polymer Physics; Cornell University Press: Ithaca, 1979.

    Google Scholar 

  23. Mirny, L. A. The fractal globule as a model of chromatin architecture in the cell.Chromosome Res.2011,19, 37–51.

    Article CAS PubMed PubMed Central  Google Scholar 

  24. Onsager, L. The effects of shape on the interaction of colloidal particles.Ann. N. Y. Acad. Sci.1949,51, 627–659.

    Article CAS  Google Scholar 

  25. Bolhuis, P.; Frenkel, D. Tracing the phase boundaries of hard spherocylinders.J. Chem. Phys.1997,106, 666–687.

    Article CAS  Google Scholar 

  26. Shundyak, K.; van Roij, R. van der Schoot, P. Theory of the isotropic-nematic transition in dispersions of compressible rods.Phys. Rev. E2006,74, 021710.

    Article  Google Scholar 

  27. Meldal, B. H. M.; Bye-A-jee, H.; Gajdoš, L.; Hammerová, Z.; Horáčková, A.; Melicher, F.; Perfetto, L.; Pokorný, D.; Lopez, M. R.; Türková, A. et al. Complex Portal 2018: Extended content and enhanced visualization tools for macromolecular complexes.Nucleic Acids Res.2019,47, D550–D558.

    Article CAS PubMed  Google Scholar 

  28. RCSB PDB.RCSB PDB [Online].https://www.rcsb.org/search (accessed Feb 1, 2022).

  29. Sartori, P.; Leibler, S. Lessons from equilibrium statistical physics regarding the assembly of protein complexes.Proc. Natl. Acad. Sci. USA2020,117, 114–120.

    Article CAS PubMed  Google Scholar 

  30. Larson, A. G.; Elnatan, D.; Keenen, M. M.; Trnka, M. J.; Johnston, J. B.; Burlingame, A. L.; Agard, D. A.; Redding, S.; Narlikar, G. J. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.Nature2017,547, 236–240.

    Article CAS PubMed  Google Scholar 

  31. Gibson, B. A.; Doolittle, L. K.; Schneider, M. W. G.; Jensen, L. E.; Gamarra, N.; Henry, L.; Gerlich, D. W.; Redding, S.; Rosen, M. K. Organization of chromatin by intrinsic and regulated phase separation.Cell2019,179, 470–484.

    Article CAS PubMed  Google Scholar 

  32. Kilic, S.; Lezaja, A.; Gatti, M.; Bianco, E.; Michelena, J.; Imhof, R.; Altmeyer, M. Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments.EMBO J.2019,38, e101379.

    Article PubMed  Google Scholar 

  33. Chong, S. S.; Dugast-Darzacq, C.; Liu, Z.; Dong, P.; Dailey, G. M.; Cattoglio, C.; Heckert, A.; Banala, S.; Lavis, L.; Darzacq, X. et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription.Science2018,361, eaar2555.

    Article PubMed  Google Scholar 

  34. Cho, W. K.; Spille, J. H.; Hecht, M.; Lee, C.; Li, C.; Grube, V.; Cisse, I. I. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates.Science2018,361, 412–415.

    Article CAS PubMed  Google Scholar 

  35. Parker, W. M.; Bell, M.; Mir, M.; Kao, J. A.; Darzacq, X.; Botchan, M. R.; Berger, J. M. A new class of disordered elements controls DNA replication through initiator self-assembly.eLife2019,8, e48562.

    Article CAS PubMed  Google Scholar 

  36. Scholl, D.; Deniz, A. A. Conformational freedom and topological confinement of proteins in biomolecular condensates.J. Mol. Biol.2022,434, 167348.

    Article CAS PubMed  Google Scholar 

  37. Shank, E. A.; Cecconi, C.; Dill, J. W.; Marqusee, S.; Bustamante, C. The folding cooperativity of a protein is controlled by its chain topology.Nature2010,465, 637–640.

    Article CAS PubMed  Google Scholar 

  38. Baker, D. A surprising simplicity to protein folding.Nature2000,405, 39–42.

    Article CAS PubMed  Google Scholar 

  39. Koga, N.; Tatsumi-Koga, R.; Liu, G. H.; Xiao, R.; Acton, T. B.; Montelione, G. T.; Baker, D. Principles for designing ideal protein structures.Nature2012,491, 222–227.

    Article CAS PubMed  Google Scholar 

  40. Ong, C. T.; Corces, V. G. CTCF: An architectural protein bridging genome topology and function.Nat. Rev. Genet.2014,15, 234–246.

    Article CAS PubMed  Google Scholar 

  41. Rapp, M.; Granseth, E.; Seppälä, S.; von Heijne, G. Identification and evolution of dual-topology membrane proteins.Nat. Struct. Mol. Biol.2006,13, 112–116.

    Article CAS PubMed  Google Scholar 

  42. Peisajovich, S. G.; Rockah, L.; Tawfik, D. S. Evolution of new protein topologies through multistep gene rearrangements.Nat. Genet.2006,38, 168–174.

    Article CAS PubMed  Google Scholar 

  43. Sato, P. M.; Yoganathan, K.; Jung, J. H.; Peisajovich, S. G. The robustness of a signaling complex to domain rearrangements facilitates network evolution.PLoS Biol.2014,12, e1002012.

    Article PubMed  Google Scholar 

  44. de Souza, N. An expanded human interactome.Nat. Methods2015,12, 107.

    Article CAS PubMed  Google Scholar 

  45. Rolland, T.; Taşan, M.; Charloteaux, B.; Pevzner, S. J.; Zhong, Q.; Sahni, N.; Yi, S.; Lemmens, I.; Fontanillo, C.; Mosca, R. et al. A proteome-scale map of the human interactome network.Cell2014,159, 1212–1226.

    Article CAS PubMed  Google Scholar 

  46. Boisvert, F. M.; van Koningsbruggen, S.; Navascués, J.; Lamond, A. I. The multifunctional nucleolus.Nat. Rev. Mol. Cell Biol.2007,8, 574–585.

    Article CAS PubMed  Google Scholar 

  47. Nepusz, T.; Yu, H. Y.; Paccanaro, A. Detecting overlapping protein complexes in protein-protein interaction networks.Nat. Methods2012,9, 471–472.

    Article CAS PubMed  Google Scholar 

  48. Spirin, V.; Mirny, L. A. Protein complexes and functional modules in molecular networks.Proc. Natl. Acad. Sci. USA2003,100, 12123–12128.

    Article CAS PubMed  Google Scholar 

  49. Ganser, L. R.; Myong, S. Methods to study phase-separated condensates and the underlying molecular interactions.Trends Biochem. Sci.2020,45, 1004–1005.

    Article CAS PubMed  Google Scholar 

  50. Cao, J.; Gong, H.; Xie, L.; Li, Y.; Zhang, N.; Tian, W.; Zhang, R.; Zhou, J.; Wang, T.; Zhai, Y. et al. Super-assembled carbon nanofibers decorated with dual catalytically active sites as bifunctional oxygen catalysts for rechargeable Zn-air batteries.Mater. Today Energy2021,20, 100682.

    Article CAS  Google Scholar 

  51. Lapenta, F.; Aupič, J.; Strmšek, Ž.; Jerala, R. Coiled coil protein origami: From modular design principles towards biotechnological applications.Chem. Soc. Rev.2018,47, 3530–3542.

    Article CAS PubMed  Google Scholar 

  52. Kočar, V.; Schreck, J. S.; Čeru, S.; Gradišar, H.; Bašić, N.; Pisanski, T.; Doye, J. P. K.; Jerala, R. Design principles for rapid folding of knotted DNA nanostructures.Nat. Commun.2016,7, 10803.

    Article PubMed PubMed Central  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Medical Systems Biophysics and Bioengineering, Leiden Academic Centre for Drug Research, Faculty of Science, Leiden University, Leiden, 2333CC, the Netherlands

    Maziar Heidari, Duane Moes, Otto Schullian, Barbara Scalvini & Alireza Mashaghi

  2. Fachbereich Physik, Freie Universität Berlin, Arnimallee 14, Berlin, 14195, Germany

    Otto Schullian

  3. Harvard Medical School, Harvard University, 25 Shattuck St, Boston, MA, 02115, USA

    Alireza Mashaghi

Authors
  1. Maziar Heidari

    You can also search for this author inPubMed Google Scholar

  2. Duane Moes

    You can also search for this author inPubMed Google Scholar

  3. Otto Schullian

    You can also search for this author inPubMed Google Scholar

  4. Barbara Scalvini

    You can also search for this author inPubMed Google Scholar

  5. Alireza Mashaghi

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toAlireza Mashaghi.

Electronic supplementary material

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heidari, M., Moes, D., Schullian, O.et al. A topology framework for macromolecular complexes and condensates.Nano Res.15, 9809–9817 (2022). https://doi.org/10.1007/s12274-022-4355-x

Download citation

Keywords

Use our pre-submission checklist

Avoid common mistakes on your manuscript.

Advertisement


[8]ページ先頭

©2009-2025 Movatter.jp