In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 83, No. 18 ( 1986-09), p. 6711-6715
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.83.18.6711
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1986
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
