title: Stall no more at polyproline stretches with the translation elongation factors EF-P and IF-5A.
abstract: Synthesis of polyproline proteins leads to translation arrest. To overcome this ribosome stalling effect, bacteria depend on a specialized translation elongation factor P (EF-P), being orthologous and functionally identical to eukaryotic/archaeal elongation factor e/aIF-5A (recently renamed 'EF5'). EF-P binds to the stalled ribosome between the peptidyl-tRNA binding and tRNA-exiting sites, and stimulates peptidyl-transferase activity, thus allowing translation to resume. In their active form, both EF-P and e/aIF-5A are post-translationally modified at a positively charged residue, which protrudes toward the peptidyl-transferase center when bound to the ribosome. While archaeal and eukaryotic IF-5A strictly depend on (deoxy-) hypusination (hypusinylation) of a conserved lysine, bacteria have evolved diverse analogous modification strategies to activate EF-P. In Escherichia coli and Salmonella enterica a lysine is extended by β-lysinylation and subsequently hydroxylated, whereas in Pseudomonas aeruginosa and Shewanella oneidensis an arginine in the equivalent position is rhamnosylated. Inactivation of EF-P, or the corresponding modification systems, reduces not only bacterial fitness, but also impairs virulence. Here, we review the function of EF-P and IF-5A and their unusual posttranslational protein modifications.
authors.affiliation: Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München, D-81377, Munich, Germany.|Department of Biology I, Microbiology, Ludwig-Maximilians-Universität München, D-82152, Martinsried, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lassak
authors.affiliation: Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München, D-81377, Munich, Germany.|Gene Center, Department for Biochemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Wilson
authors.affiliation: Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München, D-81377, Munich, Germany.|Department of Biology I, Microbiology, Ludwig-Maximilians-Universität München, D-82152, Martinsried, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Jung
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012270:Ribosomes / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D010455:Peptides; C115531:aIF-5A; C020746:factor EF-P; C011083:polyproline