Bs. Negrutskii et al., Functional interaction of mammalian valyl-tRNA synthetase with elongation factor EF-1 alpha in the complex with EF-1H, J BIOL CHEM, 274(8), 1999, pp. 4545-4550
In mammalian cells valyl-tRNA synthetase (ValRS) forms a high M-r complex w
ith the four subunits of elongation factor EF-1H. The beta, gamma, and delt
a subunits, that contribute the guanine nucleotide exchange activity of EF-
1H, are tightly associated with the NH2-terminal polypeptide extension of v
alyl-tRNA synthetase, In this study, we have examined the possibility that
the functioning of the companion enzyme EF-1 alpha could regulate valyl-tRN
A synthetase activity. We show here that the addition of EF-1 alpha and GTP
in excess in the aminoacylation mixture is accompanied by a 2-fold stimula
tion of valyl-tRNA(Val) synthesis catalyzed by the vall-tRNA synthetase com
ponent of the ValRS EF-1H complex. This effect is not observed in the prese
nce of EF-1 alpha and GDP or EF-Tu GTP and requires association of valyl-tR
NA synthetase within the ValRS EF-1H complex. Since valyl-tRNA synthetase a
nd elongation factor EF-1 alpha catalyze two consecutive steps of the in vi
vo tRNA cycle, aminoacylation and formation of the ternary complex EF-1 alp
ha.GTP.Val-tRNA(Val) that serves as a vector of tRNA from the synthetase to
the ribosome, the data suggest a coordinate regulation of these two succes
sive reactions. The EF-1 alpha.GTP-dependent stimulation of valyl-tRNA synt
hetase activity provides further evidence for tRNA channeling during protei
n synthesis in mammalian cells.