Constant trouble with prolines—navigating a global translation dilemma

Proline is a paradox in biology-integral to protein structure and functionality, yet exceptionally challenging during translation. This review examines what sets proline apart from the other proteinogenic amino acids, detailing its unique chemical and structural characteristics that hinder efficient peptide bond formation. Although proline's impact is evident across all domains of life, our focus is primarily on bacteria, where the evolutionary pressure to overcome proline-induced ribosomal stalling has led to a sophisticated suite of specialized translation factors. Ultimately, we discuss how the interplay between proline and its translational rescue systems not only ensures protein synthesis but also drives the evolution of bacterial proteomes.