Elongation factor Tu is a multifunctional and processed moonlighting protein

• Published in: Scientific reports Vol. 7; no. 1; pp. 11227 - 17
• Main Authors: Widjaja, Michael, Harvey, Kate Louise, Hagemann, Lisa, Berry, Iain James, Jarocki, Veronica Maria, Raymond, Benjamin Bernard Armando, Tacchi, Jessica Leigh, Gründel, Anne, Steele, Joel Ricky, Padula, Matthew Paul, Charles, Ian George, Dumke, Roger, Djordjevic, Steven Philip
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.09.2017; Nature Publishing Group
• Subjects: 14; 631/1647/2067; 631/326/41/2531; 82; 82/16; 82/29; 82/58; Bioinformatics; Cell surface; Codon bias; Computational Biology; Elongation; Elongation factor EF-Tu; Fibrinolysin - metabolism; Genomes; Host-Pathogen Interactions; Humanities and Social Sciences; Membrane Proteins - metabolism; Models, Molecular; multidisciplinary; Mycoplasma hyopneumoniae - enzymology; Mycoplasma hyopneumoniae - genetics; Mycoplasma pneumoniae - enzymology; Mycoplasma pneumoniae - genetics; Pathogens; Peptide Elongation Factor Tu - metabolism; Plasmin; Plasminogen - metabolism; Protein Binding; Science; Science (multidisciplinary); Staphylococcus aureus - enzymology; Staphylococcus aureus - genetics; Virulence Factors - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-10644-z

Many bacterial moonlighting proteins were originally described in medically, agriculturally, and commercially important members of the low G + C Firmicutes. We show Elongation factor Tu (Ef-Tu) moonlights on the surface of the human pathogens Staphylococcus aureus (Sa Ef-Tu ) and Mycoplasma pneumoniae (Mpn Ef-Tu ), and the porcine pathogen Mycoplasma hyopneumoniae (Mhp Ef-Tu ). Ef-Tu is also a target of multiple processing events on the cell surface and these were characterised using an N-terminomics pipeline. Recombinant Mpn Ef-Tu bound strongly to a diverse range of host molecules, and when bound to plasminogen, was able to convert plasminogen to plasmin in the presence of plasminogen activators. Fragments of Ef-Tu retain binding capabilities to host proteins. Bioinformatics and structural modelling studies indicate that the accumulation of positively charged amino acids in short linear motifs (SLiMs), and protein processing promote multifunctional behaviour. Codon bias engendered by an A + T rich genome may influence how positively-charged residues accumulate in SLiMs.