Formation of a translational inhibitor by interaction of phospholipid with the eukaryotic initiation factor 2.
- 1 September 1986
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 83 (18) , 6711-6715
- https://doi.org/10.1073/pnas.83.18.6711
Abstract
The polypeptide chain initiation factor 2 (eIF-2) binds phospholipid (PL) and becomes a potent inhibitor of translation in hemin-supplemented reticulocyte lysates. This binding is markedly reduced by prior treatment of eIF-2 with N-ethylmaleimide. Although PL is probably bound by all three eIF-2 subunits, our results suggest that the inhibitory molecule is produced by binding to the alpha subunit because, functionally, PL binding has the same effect on eIF-2 as alpha-subunit phosphorylation. This is suggested by the following findings. (i) Like translational inhibition due to heme deficiency, inhibition by small amounts of the eIF-2 X PL complex is prevented by small amounts of the GDP exchange factor (GEF). (ii) In the presence of Mg2+, the GEF-catalyzed formation of a ternary complex (eIF-2 X GTP X Met-tRNAi in which Met-tRNAi is the eukaryotic initiator methionyl tRNA) is inhibited by eIF-2 X PL just as well as by eIF-2 alpha-subunit phosphorylation. (iii) Also in the presence of Mg2+, GEF is unable to catalyze the exchange of free GDP with eIF-2 X PL-bound GDP, as it fails to catalyze the exchange of free GDP with GDP that is bound to alpha-subunit-phosphorylated eIF-2. These observations suggest that, like alpha-subunit-phosphorylated eIF-2, eIF-2 X PL traps GEF in a nondissociable eIF-2 X PL X GEF complex, whereby GEF is no longer able to catalyze ternary complex formation and initiation is inhibited.Keywords
This publication has 11 references indexed in Scilit:
- The regulation of initiation of protein synthesis by phosphorylation of eIF-2(alpha) and the role of reversing factor in the recycling of eIF-2.Journal of Biological Chemistry, 1984
- Mechanism of translational control by partial phosphorylation of the alpha subunit of eukaryotic initiation factor 2.Proceedings of the National Academy of Sciences, 1984
- Activation of the heme-stabilized translational inhibitor of reticulocyte lysates by calcium ions and phospholipid.Proceedings of the National Academy of Sciences, 1983
- Regulation of protein synthesis initiation in eucaryotesArchives of Biochemistry and Biophysics, 1983
- Effect of phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 on the function of reversing factor in the initiation of protein synthesis.Proceedings of the National Academy of Sciences, 1983
- Initiation of protein synthesis in eukaryotes. Nature of ternary complex dissociation factor.Journal of Biological Chemistry, 1982
- Mechanism of polypeptide chain initiation in eukaryotes and its control by phosphorylation of the alpha subunit of initiation factor 2.Proceedings of the National Academy of Sciences, 1982
- Phosphorylation inhibits guanine nucleotide exchange on eukaryotic initiation factor 2Nature, 1982
- Mode of action of the heme-controlled translational inhibitor: relationship of eukaryotic initiation factor 2-stimulating protein to translation restoring factor.Proceedings of the National Academy of Sciences, 1981
- Further studies on the mode of action of the heme-controlled translational inhibitor.Proceedings of the National Academy of Sciences, 1979