Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Eviatar Natan, Tamaki Endoh, Liora Haim-Vilmovsky, Tilman Flock, Guilhem Chalancon, Jonathan T.S. Hopper, Bálint Kintses, Peter Horvath, Lejla Daruka, Gergely Fekete, Csaba Pál, Balázs Papp, Erika Oszi, Zoltán Magyar, Joseph A. Marsh, Adrian H. Elcock, M. Madan Babu, Carol V. Robinson, Naoki Sugimoto, Sarah A. Teichmann

Research output: Article

8 Citations (Scopus)


Cotranslational protein folding can facilitate rapid formation of functional structures. However it can also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. By analyzing known protein structures, we show that homomeric protein contacts are enriched toward the C termini of polypeptide chains across diverse proteomes. We hypothesize that this is the result of evolutionary constraints for folding to occur before assembly. Using high-throughput imaging of protein homomers in Escherichia coli and engineered protein constructs with N- and C-terminal oligomerization domains, we show that, indeed, proteins with C-terminal homomeric interface residues consistently assemble more efficiently than those with N-terminal interface residues. Using in vivo, in vitro and in silico experiments, we identify features that govern successful assembly of homomers, which have implications for protein design and expression optimization.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalNature Structural and Molecular Biology
Issue number3
Publication statusPublished - márc. 1 2018

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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  • Cite this

    Natan, E., Endoh, T., Haim-Vilmovsky, L., Flock, T., Chalancon, G., Hopper, J. T. S., Kintses, B., Horvath, P., Daruka, L., Fekete, G., Pál, C., Papp, B., Oszi, E., Magyar, Z., Marsh, J. A., Elcock, A. H., Babu, M. M., Robinson, C. V., Sugimoto, N., & Teichmann, S. A. (2018). Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins. Nature Structural and Molecular Biology, 25(3), 279-288.