Hingey, J. M.; Rudolfs, B.; Haack, D. B.; Murphy, F. V.; Joseph, S.; Toor, N.

Ribosomes synthesize proteins with an RNA-only active site across all kingdoms of life. Yet, despite decades of high-resolution ribosome structures, the precise catalytic mechanism has remained elusive. Here, we provide structural evidence for metal ion involvement in peptide bond formation, drawn from ribosome structures spanning bacteria, archaea, and eukaryotes. The metal ion resides in the active site, adjacent to a universally conserved stack of three base triples, reminiscent of the catalytic triplex in group II introns and the spliceosome, which catalyze pre-mRNA splicing. Metal-ion catalysis thus emerges as a fundamental unifying theme across the central dogma spanning protein synthesis, RNA splicing, and nucleic acid replication.