Aminoacyl-tRNA synthetases are a family of enzymes which play an indispensable role in the initial steps of protein biosynthesis by catalyzing the formation of aminoacyl-tRNA from amino acid, cognate tRNA and ATP by highly selective intermolecular interactions. Several enzymes of this family occur as free soluble enzymes in bateria, but as multi-enzyme complexes in mammalian cells. Preliminary structural characterization of the aminoacyl-tRNA synthetase complexes has been carried out. The function of the association of synthetases is not at all understood. The proposed research plans to analyze the structure and the function of the synthetase complexes. In the structural analysis, the subunit structures of individual synthetases in the synthetase complex will be determined by physical characterization of purified synthetases, affinity labeling and immunochemical methods, and the spatial arrangement of different proteins in the synthetase complex will be examined by immuno-inhibition, chemical cross-linking and electron microscopy. In the functional analysis, we plan to investigate the possible presence of regulatory factors or channeling mechanisms in the synthetase complex, the structural and functional interaction of synthetase complexes with other components in protein biosynthesis, and to survey the presence of any proteins with known functions in the synthetase complexes. These studies may provide fundamental principles in the higher order of structural organization of proteins and a quantitative assessment of the function of such protein structure during evolution.
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