Structural evidence for metal ion catalysis in the ribosome

Abstract

Ribosomes synthesize proteins with an RNA-only active site across all domains of life, yet the details of the catalytic mechanism have remained elusive despite decades of high-resolution ribosome structures. Here, we provide structural evidence for the involvement of two metal ions in peptide bond formation, drawn from ribosome structures spanning bacteria, archaea, and eukaryotes. These metal ions reside in the peptidyl transferase center, one of them adjacent to a universally conserved stack of three base triples, reminiscent of the catalytic triplex in group I/II introns and the spliceosome, which catalyze pre-mRNA splicing. The second metal ion is positioned to stabilize the oxyanion of the tetrahedral intermediate. Metal ion catalysis thus emerges as a recurring mechanistic theme across the central dogma spanning protein synthesis, RNA splicing, and nucleic acid replication.