A metal‐binding motif implicated in RNA recognition by an aminoacyl‐tRNA synthetase and by a retroviral gene product

Abstract

SummaryA randomly generated mutation in Escherichia coli alanine tRNA synthetase compensates for a mutation in its cognate tRNA. The enzyme's mutation occurs next to a Cys-Xj-Cys-Xg-His-Xz-His metal-binding motif that is distinct from the zinc finger motif found in some DNA-binding proteins. Instead, the synthetase's metal binding domain resembles the Cys-X2-Cys-X4-His-X4-Cys metal-binding domain of the gag gene product of retroviruses. For Ala-tRNA synthetase, the metal bound at the Cys-His motif is important specifically for the tRNA-dependent step of catalysis, and the enzyme-tRNA interaction is dependent on the geometry of metal co-ordination to the enzyme. These data, and the demonstrated sensitivity of RNA packaging to mutations in the metal-binding domain of the gag gene product of retroviruses, suggest that an aminoacyl-tRNA synthetase and retroviruses have adopted a related metal-binding motif for RNA recognition. Mutations that affect RNA specificity in an aminoacyl-tRNA synthetase and in retrovirusesThe fidelity of protein biosynthesis is maintained by specific transfer RNA recognition by aminoacyl-tRNA synthetases. These enzymes catalyse the attachment of amino acids to their cognate tRNAs (Schimmel, 1987). Recent investigations have focused on the identification of specific protein-RNA contacts that contribute to tRNA discrimination. Mutations that alter tRNA recognition have been characterized in the Met-, Gin-, and Ala-tRNA synthetases (Perona etal., 1989; Meinnel etal., 1991; Miller ef a/., 1991a).

X-ray Absorption Spectroscopy of the Zinc Site in tRNA-Guanine Transglycosylase from Escherichia coli

“…These motifs usually contain two cysteine and two histidine residues that ligand to the zinc ion in a tetrahedral fashion. More recently four cysteine and three cysteine/one histidine type zinc-finger motifs have been found in proteins that bind to RNA (Miller & Schimmel, 1992). The exact role of the zinc-finger motifs in RNA-binding proteins is still unclear.…”

An isoleucyl-tRNA synthetase gene from Campylobacter jejuni

“…3). This C, box is assumed to function in metal binding during tRNA aminoacylation (Miller & Schimmel, 1992). Another putative consensus at the C-terminus is a single amino acid K which is correspondingly located at amino acid 736 in C.jejmi IleRS, at amino acid 726 in Staph.…”