EUKARYOTIC TRANSLATION ELONGATION-FACTOR 1-GAMMA CONTAINS A GLUTATHIONE TRANSFERASE DOMAIN - STUDY OF A DIVERSE, ANCIENT PROTEIN SUPERFAMILY USING MOTIF SEARCH AND STRUCTURAL MODELING

Using computer methods for multiple alignment, sequence motif search, and tertiary structure modeling, we show that eukaryotic translation e longation factor 1 gamma (EF1 gamma) contains an N-terminal domain rel ated to class theta glutathione S-transferases (GST). GST-Iike protein s related to class theta comprise a large group including, in addition to typical GSTs and EF1 gamma, stress-induced proteins from bacteria and plants, bacterial reductive dehalogenases and beta-etherases, and several uncharacterized proteins. These proteins share 2 conserved seq uence motifs with GSTs of other classes (alpha, mu, and pi). Tertiary structure modeling showed that in spite of the relatively low sequence similarity, the GST-related domain of EF1 gamma is likely to form a f old very similar to that in the known structures of class alpha, mu, a nd pi GSTs. One of the conserved motifs is implicated in glutathione b inding, whereas the other motif probably is involved in maintaining th e proper conformation of the GST domain. We predict that the GST-like domain in EF1 gamma is enzymatically active and that to exhibit GST ac tivity, EF1 gamma has to form homodimers. The GST activity may be invo lved in the regulation of the assembly of multisubunit complexes conta ining EF1 and aminoacyl-tRNA synthetases by shifting the balance betwe en glutathione, disulfide glutathione, thiol groups of cysteines, and protein disulfide bonds. The GST domain is a widespread, conserved enz ymatic module that may be covalently or noncovalently complexed with o ther proteins. Regulation of protein assembly and folding may be 1 of the functions of GST.