Polypeptide chain elongation

Dias N., Dheur S., Nielsen P.E., Gryaznov S., Van Aerschot A., Herde-wijN P., Helene G., Saison-Behmoaras T. E. Antisense PNA tridecamers targeted to the coding region of Ha-ras mRNA arrest polypeptide chain elongation. J. Mol. Biol. 1999 294 403-416. 

Tokumoto, T. et al. Regulated interaction between polypeptide chain elongation factor-1 complex with the 26S proteasome during Xenopus oocyte maturation. BMC Biochem 2003, 4, 6. 

Figure 7 The direct and indirect pathways of tRNA asparaginylation. The direct pathway consists of charging by AsnRS on tRNA " of free Asn formed with asparagine synthetase A or B. The Asn-tRNA " binds the EF-Tu factor in bacteria (or EF-1A in eukaryotes and archaea) to be carried to the ribosome, in the indirect pathway, a nondiscriminating AspRS (ND-AspRS) charges Asp on tRNA " Asp-tRNA " does not bind the eiongation factor but is converted by the tRNA-dependent trimeric amidotransferase GatCAB into Asn-tRNA ", which binds the EF-Tu factor and is carried to the ribosome where it is used for polypeptide chain elongation.

Most mutations represent the replacement of one base by another a minority is caused by deletions of some base pairs, by frameshift, by polypeptide chain elongation due to mutation of a terminator codon, or by recombinational events with mutation-like effects. The replacement of one base for another is currently indicated by the term single-nucleotide polymorphism, abbreviated as SNP. It occurs at a frequency of roughly one per every 500-1000 base pairs of genomic DNA, which means that most genes carry one or two SNPs, although many are without any functional significance. ... 

Figure 2. Schematic representation of the cycl ic and repetitive event of polypeptide chain elongation. Numbers in O represent various elongation factors, o represents aminoacyl-tRNA, and a represents the amino acid. (From Johansen and Rattan, 1993).

EF-2 is a GTP-binding protein. When it is ADP-ribosylated, it cannot mediate polypeptide-chain elongation, consequently the affected cells lose the ability to synthesize protein and die. 

It is known that protein synthesis is necessary for BR-induced effects in root tissue (25), and BR-treatment increases nucleic acid and protein synthesis in bean stem (26). In the pea stem segment, kinetic studies with selected protein and nucleic acid synthesis inhibitors showed no evidence for competitive inhibition in polypeptide chain elongation, post-transcriptional polyA addition to heterogeneous RNA, DNA-dependent RNA synthesis, or of the DNA-dependent RNA polymerase... 

Enzyme ReguL 19, 427 (1980). Effect on polypeptide chain elongation in vitro A. K. Abraham, A. Pihl, Eur. J. Biochem 106, 257 (1980). Regulation of tRNA methyl transferase activity M. Mach et aL, Biochem J. 202, 153 (1982). HPLC study C. E. Prussak, D. H. Russell, J. Chromatog. 229, 47 (1982). Interaction with actin, q.v. C. Oriol-Audit, Biochem. Biophys. Res. Commun. 105, 1096 (1982). Studies on use as a biochemical tool in career research A. Thyss et L, Eur. J- Cancer Clin, OncoL 18, 611 (1982) V, Quemener... 

To this point, you have become familiar with the molecules that participate in protein synthesis and the genetic code, the language that directs the synthesis. We now investigate the actual process by which polypeptide chains are assembled. There are three major stages in protein synthesis initiation of the polypeptide chain, elongation of the chain, and termination of the completed polypeptide chain. 

Cells incubated in medium without one or all of the essential amino acids also show a decline in protein synthesis over the first hour, involving an inhibition of both polypeptide chain elongation and initiation (Van Venrooij et al., 1972 Vaughan et al, 1971). Inhibition is fully reversible on readdition of the amino acid(s), even in the presence of actinomycin D, and, again, initiation appears to be the more sensitive of the two steps. It is not known whether this effect is a result of some general control of the rate of initiation by the intracellular level of all 20 amino acids or their charged tRNA s, or whether it is an indirect result of a decrease in the level of ATP (Van Venrooij et al, 1972). 

MATHEWS, M.B. and OSBORE, M. The rate of polypeptide chain elongation in a cell-free system from Krebs II ascites cells. Biochem. Biophys. Acta. (1974)> 340t 147-152. 

To eliminate exonucleolytic attack as a cause of mRNA degradation we followed the fate of mRNA stably attached to ribosomes. If an inhibitor of polypeptide chain elongation is added to the incubations to prevent ribosome movement along mRNA, breakdown of polysomes can only result from endonucleolytic cleavage of the mRNA strand connecting ribosomes. Figure 2 shows... 

Blasticidins pyrimidine antibiotics synthesized by Streptomyces griseochromogenes (see Nucleoside antibiotics). They inhibit the growth of fungi, e.g. the rice fungus, Piricularia oryzae, and a few bacteria. The antibiotic effect is due to suppression of polypeptide chain elongation during protein biosynthesis. 

Regulatory mechanisms at the level of mRNA translation could also lead to gross metabolic changes. The mechanism of protein synthesis has been exhaustively studied [5], and many components have been implicated. Changes in each of these components—ribosomes, factors involved in the ribosomal binding of mRNA, in the initiation and termination of protein synthesis, and in polypeptide chain elongation, tRNA, and the components responsible for its acylation and subsequent transfer to the polysomal complex—could potentially lead to alteration in the rate, extent, or fidelity of protein synthesis. 

STUDIES ON THE POLYPEPTIDE CHAIN ELONGATION AND A CHALLENGE TO MECHANOCHEMICAL REACTIONS... 

Figure 1 summarizes the current knowledge of polypeptide chain elongation reactions in E. coli. The three protein factors, EF-Tu, EF-Ts and EF-G, are involved in these reactions. The complex of EF-Tu and EF-Ts, the EF-Tu EF-Ts complex, reacts with GTP... 

Arai, K., Arai, T., Kawakita, M. and Kaziro, Y. (1975) Conformational transitions of polypeptide chain elongation factor Tu. I. Studies with hydrophobic probes. J. Biochem. Tokyo), 77, 1095-1106. 

Fio. 1. Polypeptide chain elongation. Description of the partial reactions is described in the text. tRNA is designated as a dark bar. The elongation factors are referred to as Tu, Ts and G. 

As traiislation progresses, the ribosome moves from the S -phosphate end to the 3 -OH end of messenger RNA whilst the polypeptide chain elongates. When the S end of the messenger RNA is sterically free, synthesis of a new polypeptide may be initiated. In this mamm, the translating machinery becomes able to realize... 

Ballinger, D. G., and Pardue, M. L., 1983, The control of protein synthesis during heat shock in Drosophila cells involves altered polypeptide chain elongation rates. Cell 33 103. 

Kaziro, Y., 1978, The role of guanosine 5 -triphosphate in polypeptide chain elongation, Biochim. Biophys. Acta 505 95. 

Thomas, G. P., and Mathews, M. B., 1982, Control of polypeptide chain elongation in the stress response A novel translational control, in Heat Shock, from Bacteria to Man (M. J. Schlesinger, M. Ashburner, and A. Tissieres, eds.), pp. 207-213, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. 

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