IDEAS home Printed from https://ideas.repec.org/a/plo/pcbi00/1006886.html
   My bibliography  Save this article

Evolution of interface binding strengths in simplified model of protein quaternary structure

Author

Listed:
  • Alexander S Leonard
  • Sebastian E Ahnert

Abstract

The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new idealized framework to facilitate the study of protein self-assembly processes and their evolution.Author summary: Protein complexes assemble by joining individual proteins together through interacting binding sites. Because of the long time scales of biological evolution, it can be difficult to reconstruct how these interactions change over time. We use simplified representations of proteins to simulate the evolution of these complexes on a computer. In some cases the order in which the complex assembles is crucial. We show that biological evolution increases the strength of interactions that must occur earlier, and decreases the strength of later interactions. Similar knowledge of interactions being preferred to be stronger or weaker can also help to predict the evolutionary ancestry of a complex. While these simulations are too idealized to make exact predictions, this general link between ordered pathways in assembly and evolution matches well-established observations that have been made in real protein complexes. This means that our model provides a powerful framework to help study protein complex assembly and evolution.

Suggested Citation

  • Alexander S Leonard & Sebastian E Ahnert, 2019. "Evolution of interface binding strengths in simplified model of protein quaternary structure," PLOS Computational Biology, Public Library of Science, vol. 15(6), pages 1-15, June.
  • Handle: RePEc:plo:pcbi00:1006886
    DOI: 10.1371/journal.pcbi.1006886
    as

    Download full text from publisher

    File URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006886
    Download Restriction: no

    File URL: https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006886&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pcbi.1006886?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Hector Garcia-Seisdedos & Charly Empereur-Mot & Nadav Elad & Emmanuel D. Levy, 2017. "Proteins evolve on the edge of supramolecular self-assembly," Nature, Nature, vol. 548(7666), pages 244-247, August.
    2. Emmanuel D. Levy & Elisabetta Boeri Erba & Carol V. Robinson & Sarah A. Teichmann, 2008. "Assembly reflects evolution of protein complexes," Nature, Nature, vol. 453(7199), pages 1262-1265, June.
    3. Joseph A. Marsh & Holly A. Rees & Sebastian E. Ahnert & Sarah A. Teichmann, 2015. "Structural and evolutionary versatility in protein complexes with uneven stoichiometry," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Christin Pohl & Gregory Effantin & Eaazhisai Kandiah & Sebastian Meier & Guanghong Zeng & Werner Streicher & Dorotea Raventos Segura & Per H. Mygind & Dorthe Sandvang & Line Anker Nielsen & Günther H., 2022. "pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Johannes Venezian & Hagit Bar-Yosef & Hila Ben-Arie Zilberman & Noam Cohen & Oded Kleifeld & Juan Fernandez-Recio & Fabian Glaser & Ayala Shiber, 2024. "Diverging co-translational protein complex assembly pathways are governed by interface energy distribution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Lauren Ann Metskas & Davi Ortega & Luke M. Oltrogge & Cecilia Blikstad & Derik R. Lovejoy & Thomas G. Laughlin & David F. Savage & Grant J. Jensen, 2022. "Rubisco forms a lattice inside alpha-carboxysomes," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    4. Eric M. Lynch & Heather Hansen & Lauren Salay & Madison Cooper & Stepan Timr & Justin M. Kollman & Bradley A. Webb, 2024. "Structural basis for allosteric regulation of human phosphofructokinase-1," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pcbi00:1006886. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: ploscompbiol (email available below). General contact details of provider: https://journals.plos.org/ploscompbiol/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.