Regulation of ternary (Met-tRNAf - GTP - eukaryotic initiation factor 2) protein synthesis initiation complex formation by the adenylate energy charge.
Formation of the ternary [Met-tRNAf - GTP - eukaryotic initiation factor 2] protein synthesis initiation complex in rabbit reticulocyte ribosomal eluates is dependent on the GTP: GDP ratio and on the adenylate energy charge. The elements controlling ternary initiation complex formation have been studied in a reconstituted system contianing eukaryotic initiation factor 2 and nucleoside diphosphate kinase purified from the ribosomal eluate. The concentration of GTP required for half maximal formation of the ternary initiation complex is 2.5 - 10(6) M; GDP is a potent competitive inhibitor with Ki equals 3.4 - 10(7) M. Sensitive control of ternary initiation complex formation by the adenylate energy charge occurs through nucleoside diphosphate kinase regulation of the GTP : GDP ratio. Over a wide range of GTP : GDP ratios, 50% of maximal ternary initiation complex formation is observed at an adenylate energy charge of 0.85-0.90 resembling that seen in the unfractionated system. Small changes in adenylate energy charge near this value result in significant changes in the extent of ternary initiation complex formation. Since GTP is continually hydrolyzed to GDP during protein synthesis and since GDP is a competitive inhibitor of GTP binding to several of the protein factors necessary for mRNA translation, the synthetic process provides sensitive control by product inhibition. Ribosome-associated nucleoside diphosphate kinase control of GTP regeneration in response to the adenylate energy charge provides one mechanism for linking protein synthesis to the nutrient state and energy charge of the cell.
D000263:Adenylate Kinase / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004735:Energy Transfer; D006150:Guanine Nucleotides / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008715:Methionine; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010448:Peptide Initiation Factors; D011485:Protein Binding; D012343:RNA, Transfer / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism
D006150:Guanine Nucleotides; D046911:Macromolecular Substances; D010448:Peptide Initiation Factors; D006160:Guanosine Triphosphate; D012343:RNA, Transfer; D008715:Methionine; D000263:Adenylate Kinase