Regulation of protein synthesis in eukaryotes. Mode of action of eRF, an eIF-2-recycling factor from rabbit reticulocytes involved in GDP/GTP exchange.
The rate of initiation of protein synthesis appears to be controlled at the level of recycling of eIF-2. In this process a new factor, designated eRF, plays an important role. The factor has been purified from the post-ribosomal supernatant and has been called formerly anti-HRI and anti-inhibitor [Amesz, H., Goumans, H., Haubrich-Morree, Th., Voorma, H.O., and Benne, R. (1979) Eur. J. Biochem. 98, 513-520]. Its effect on the initiation of protein synthesis has been studied in several assays: a small but distinct effect is found in the assay for the formation of a ternary complex between eIF-2, GTP and Met-tRNA; a 4-5-fold stimulation is obtained in assays for 40S preinitiation complex formation and in the methionyl-puromycin reaction. In the latter assay a catalytic use of eIF-2 occurs provided that eRF is present. eRF forms a complex with eIF-2 which results in a decrease of the affinity of eIF-2 for GDP, giving it the properties of a GDP/GTP exchange factor. The model stresses the catalytic use of eIF-2 in initiation provided that conditions are met for GDP/GTP exchange by a transient complex formation between eIF-2 and eRF. On the other hand, it is shown that phosphorylation of eIF-2 by the hemin-regulated inhibitor (HRI) abolishes the recycling of eIF-2, by the formation of another stable complex comprising eIF-2 alpha P, GDP and eRF.
D000818:Animals; D001345:Autoradiography; D002384:Catalysis; D055598:Chemical Phenomena; D002621:Chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D015852:Eukaryotic Initiation Factor-2; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational; D010448:Peptide Initiation Factors / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011691:Puromycin / Q000031:analogs & derivatives / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*; D019892:eIF-2 Kinase
D015852:Eukaryotic Initiation Factor-2; D006150:Guanine Nucleotides; D010448:Peptide Initiation Factors; D011506:Proteins; D012346:RNA, Transfer, Amino Acyl; C026464:tRNA(m)(Met), methionine-; D006153:Guanosine Diphosphate; D011691:Puromycin; C024777:methionylpuromycin; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase