A retroviral-like metal binding motif in an aminoacyl-tRNA synthetase is important for tRNA recognition

The gag genes of retroviruses encode nucleocapsid proteins that package genomic RNA and are essential for viral infectivity. These RNA binding proteins have a Cys-Xaa₂Cys-Xaa₄-His-Xaa₄-Cys zinc binding motif that is distinct from the typical zinc-finger motif Cys-Xaa₂-Cys-Xaa_12-14-His-Xaa₂His that is found in some transcriptional activators. Escherichia coli alanyl-tRNA synthetase contains a zinc-binding Cys-Xaa₂Cys-Xaa₆-His-Xaa₂-His motif that resembles that of retroviral nucleic acid binding proteins. We show here that, for alanyl-tRNA synthetase, the metal bound at the retroviral-like metal binding motif is important specifically for tRNA recognition and not for amino acid activation. Moreover, the enzyme-tRNA interaction is strongly dependent on the geometry of metal coordination to the protein. These and additional experiments collectively suggest a role for the retroviral-like metal binding motif in RNA recognition and, further, raise the possibility that the protein-bound metal itself participates in an RNA interaction.