A recurrent magnesium-binding motif provides a framework for the ribosomal peptidyl transferase center

Abstract

The ribosome is an ancient macromolecular machine responsible for the synthesis of all proteins in all living organisms. Here we demonstrate that the ribosomal peptidyl transferase center (PTC) is supported by a framework of magnesium microclusters (Mg2+-μc's). Common features of Mg2+-μc's include two paired Mg2+ ions that are chelated by a common bridging phosphate group in the form Mg(a)2+–(O1P-P-O2P)–Mg(b)2+. This bridging phosphate is part of a 10-membered chelation ring in the form Mg(a)2+–(OP-P-O5′-C5′-C4′-C3′-O3′-P-OP)–Mg(a)2+. The two phosphate groups of this 10-membered ring are contributed by adjacent residues along the RNA backbone. Both Mg2+ ions are octahedrally coordinated, but are substantially dehydrated by interactions with additional RNA phosphate groups. The Mg2+-μc's in the LSU (large subunit) appear to be highly conserved over evolution, since they are unchanged in bacteria (Thermus thermophilus, PDB entry 2J01) and archaea (Haloarcula marismortui, PDB entry 1JJ2). The 2D elements of the 23S rRNA that are linked by Mg2+-μc's are conserved between the rRNAs of bacteria, archaea and eukarya and in mitochondrial rRNA, and in a proposed minimal 23S-rRNA. We observe Mg2+-μc's in other rRNAs including the bacterial 16S rRNA, and the P4–P6 domain of the tetrahymena Group I intron ribozyme. It appears that Mg2+-μc's are a primeval motif, with pivotal roles in RNA folding, function and evolution.