Impact of C-terminal amino acid composition on protein expression in bacteria

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  • dc.contributor.author Weber, Marc
  • dc.contributor.author Burgos, Raul
  • dc.contributor.author Yus, Eva
  • dc.contributor.author Yang, Jae-Seong
  • dc.contributor.author Lluch-Senar, Maria 1982-
  • dc.contributor.author Serrano Pubull, Luis, 1982-
  • dc.date.accessioned 2020-10-20T05:53:33Z
  • dc.date.available 2020-10-20T05:53:33Z
  • dc.date.issued 2020
  • dc.description.abstract The C-terminal sequence of a protein is involved in processes such as efficiency of translation termination and protein degradation. However, the general relationship between features of this C-terminal sequence and levels of protein expression remains unknown. Here, we identified C-terminal amino acid biases that are ubiquitous across the bacterial taxonomy (1,582 genomes). We showed that the frequency is higher for positively charged amino acids (lysine, arginine), while hydrophobic amino acids and threonine are lower. We then studied the impact of C-terminal composition on protein levels in a library of Mycoplasma pneumoniae mutants, covering all possible combinations of the two last codons. We found that charged and polar residues, in particular lysine, led to higher expression, while hydrophobic and aromatic residues led to lower expression, with a difference in protein levels up to fourfold. We further showed that modulation of protein degradation rate could be one of the main mechanisms driving these differences. Our results demonstrate that the identity of the last amino acids has a strong influence on protein expression levels.
  • dc.description.sponsorship This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 634942 (MycoSynVac) and 670216 (MYCOCHASSIS). ML-S acknowledges the support from FEDER project from Instituto Carlos III (ISCIII, Acción Estratégica en Salud 2016) (reference CP16/00094)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Weber M, Burgos R, Yus E, Yang JS, Lluch-Senar M, Serrano L. Impact of C-terminal amino acid composition on protein expression in bacteria. Mol Syst Biol. 2020 May; 16(5): e9208. DOI: 10.15252/msb.20199208
  • dc.identifier.doi http://dx.doi.org/10.15252/msb.20199208
  • dc.identifier.issn 1744-4292
  • dc.identifier.uri http://hdl.handle.net/10230/45514
  • dc.language.iso eng
  • dc.publisher EMBO Press
  • dc.relation.ispartof Molecular Systems Biology. 2020 May;16(5):e9208
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634942
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
  • dc.rights © 2020 Marc Weber et al. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Proteïnes
  • dc.subject.other Bacteris
  • dc.title Impact of C-terminal amino acid composition on protein expression in bacteria
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion