Ribosome stalling at diprolyl motifs is alleviated by elongation factor P

Abstract

During translation, amino acids are not incorporated into the growing nascent polypeptide chain at the same rates. In fact, distinct amino acid sequences are even known to cause translational arrest, for example, proline acts as both a poor donor and acceptor during peptide bond formation and a stretch of three or more consecutive prolines leads to ribosomal stalling. Ribosomes stalled on polyproline stretches are recognized by elongation factor P (EF-P), which stimulates peptide bond formation and relieves the translational stall. EF-P is posttranslationally modified by sequential action of YjeK, YjeA, and YfcM, and the modification of EF-P is crucial for its ability to alleviate ribosomal stalling. Numerous Escherichia coli proteins involved in survival under hostile conditions contain polyproline stretches, suggesting their expression is dependent on EF-P activity. Consistently, EF-P has been shown to be critical for bacterial fitness, motility, membrane integrity, stress response and virulence. Archaeal/eukaryotic initiation factor 5A (a/eIF5A) is a homologue of EF-P, which is posttranslationally modified with a hypusine moiety. In eukaryotes, thousands of proteins contain polyproline stretches, suggesting that EF-P and a/eIF5A mediate translation regulation of multiple pathways across all domains of life.