Large protein complex interfaces have evolved to promote cotranslational assembly

Abstract
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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

1. Bertolini M
2. et al
(2021) Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly
N/A.

https://www.science.org/doi/suppl/10.1126/science.abc7151/suppl_file/abc7151_table_s1.xlsx
1. Humphreys IR
2. et al
(2021) Computed structures of core eukaryotic protein complexes
ModelArchive.

https://modelarchive.org/doi/10.5452/ma-bak-cepc
1. Jumper JE
2. et al
(2021) Homo sapiens AlphaFold structures
AlphaFold Database.

https://alphafold.ebi.ac.uk/download
(2021) hu.MAP 2.0: integration of over 15,000 proteomic experiments builds a global compendium of human multiprotein assemblies'
hu.MAP 2.0.

http://humap2.proteincomplexes.org/
1. Clamer M
2. Bernabò P
3. Lauria F
4. Tebaldi T
5. Viero G
(2018) Active ribosome profiling with RiboLace and standard ribosome profiling in HEK-293 cells
NCBI Gene Expression Omnibus, GSE112353.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112353
1. Clamer M
2. et al
(2017) The SWISS-MODEL Repository-new features and functionality'
SWISS-MODEL Repository.

https://swissmodel.expasy.org/repository/species/9606
(2016) Towards consensus gene ages
N/A.

https://github.com/marcottelab/Gene-Ages

Article and author information

Author details

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.
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.

"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.

Copyright

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.