Large protein complex interfaces have evolved to promote cotranslational assembly

  1. Mihaly Badonyi
  2. Joseph A Marsh  Is a corresponding author
  1. University of Edinburgh, United Kingdom

Abstract

Assembly pathways of protein complexes should be precise and efficient to minimise misfolding and unwanted interactions with other proteins in the cell. One way to achieve this efficiency is by seeding assembly pathways during translation via the cotranslational assembly of subunits. While recent evidence suggests that such cotranslational assembly is widespread, little is known about the properties of protein complexes associated with the phenomenon. Here, using a combination of proteome-specific protein complex structures and publicly available ribosome profiling data, we show that cotranslational assembly is particularly common between subunits that form large intermolecular interfaces. To test whether large interfaces have evolved to promote cotranslational assembly, as opposed to cotranslational assembly being a non-adaptive consequence of large interfaces, we compared the sizes of first and last translated interfaces of heteromeric subunits in bacterial, yeast, and human complexes. When considering all together, we observe the N-terminal interface to be larger than the C-terminal interface 54% of the time, increasing to 64% when we exclude subunits with only small interfaces, which are unlikely to cotranslationally assemble. This strongly suggests that large interfaces have evolved as a means to maximise the chance of successful cotranslational subunit binding.

Data availability

Data and code to reproduce the results have been deposited on the OSF at https://osf.io/x5b2n/

The following previously published data sets were used

Article and author information

Author details

  1. Mihaly Badonyi

    MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Joseph A Marsh

    MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    joseph.marsh@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4132-0628

Funding

Biotechnology and Biological Sciences Research Council (BB/M010996/1)

  • Mihaly Badonyi

Medical Research Council (MR/M02122X/1)

  • Joseph A Marsh

Lister Institute of Preventive Medicine

  • Joseph A Marsh

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Marina V Rodnina, Max Planck Institute for Multidisciplinary Sciences, Germany

Publication history

  1. Received: April 20, 2022
  2. Accepted: July 27, 2022
  3. Accepted Manuscript published: July 28, 2022 (version 1)

Copyright

© 2022, Badonyi & Marsh

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. Mihaly Badonyi
  2. Joseph A Marsh
(2022)
Large protein complex interfaces have evolved to promote cotranslational assembly
eLife 11:e79602.
https://doi.org/10.7554/eLife.79602

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