title: A retroviral-like metal binding motif in an aminoacyl-tRNA synthetase is important for tRNA recognition.
abstract: 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-Xaa2-Cys-Xaa4-His-Xaa4-Cys zinc binding motif that is distinct from the typical zinc-finger motif Cys-Xaa2-Cys-Xaa12-14-His-Xaa2-His that is found in some transcriptional activators. Escherichia coli alanyl-tRNA synthetase contains a zinc-binding Cys-Xaa2-Cys-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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: W T
authors.initials: WT
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Schimmel
mesh_terms: D000412:Alanine-tRNA Ligase / Q000378:metabolism*; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D001051:Apoenzymes / Q000378:metabolism; D001665:Binding Sites; D003035:Cobalt / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D015683:Gene Products, gag / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D012343:RNA, Transfer / Q000378:metabolism*; D013379:Substrate Specificity; D015032:Zinc / Q000494:pharmacology
chemical_list: D001051:Apoenzymes; D015683:Gene Products, gag; D003035:Cobalt; D012343:RNA, Transfer; D006861:Hydrogen Peroxide; D000604:Amino Acyl-tRNA Synthetases; D000412:Alanine-tRNA Ligase; D015032:Zinc