Elongation factor interaction with ribosomes

Bermek E (1976) Interactions of adenosine diphosphate-ribosylated elongation factor 2 with ribosomes. J Biol Chem 251 6544-6549... 

Initiation (Figs. 29-10 and 29-11), elongation (Fig. 29-12), and termination are three distinct steps in the synthesis of a protein. A variety of specialized proteins are required for each stage of synthesis. Their sequential interaction with ribosomes can be viewed as a means of ensuring an orderly sequence of steps in the synthesis cycle. The rate of protein formation will depend upon the concentrations of amino acids, tRNAs, protein factors, numbers of ribosomes, and kinetic constants. The formation of specific proteins can also be inhibited by translational repressors, proteins that compete with ribosomes for binding to target mRNAs.287... 

Transfer RNAs need common features for their interactions with ribosomes and elongation factors but unique features for their interactions with the activating enzymes. 

The same method has been applied to measure the Eli domain orientation when the protein is in complex with its RNA parmer or both RNA and thiostrepton antibiotic. The additional RDCs revealed a rearrangement of the N-terminal domain of Ell placing it closer to the RNA after binding of thiostrepton. HADDOCK has been used to calculate a model of the ternary stmcture of the Ell protein in complex with RNA and antibiotic. Based on the orientational data, the dynamics and the docking model, it seems that thiostrepton locks the domain conformation of Ell in a rigid (inhibitory) state. The antibiotic thiostrepton interferes with the interaction of elongation factors to this Ell-RNA region, which has a dramatic effect on the level of protein synthesis by the ribosome. 

Bacteria and eucarya are differentially affected by antibiotics that impair ribosome function (and/or fidelity) by directly interacting with, or by perturbing, functionally essential domains of ribosomes and factors. On the basis of their specificity, ribosome-directed and elongation factor-directed antibiotics have been classically subdivided into... 

Brigotti, M., Rambelli, F., Zamboni, M., Montanaro, L. and Sperti, S. (1989) Effect of alpha-sarcin and ribosome-inactivating proteins on the interaction of elongation factors with ribosomes. Biochem J. 257, 723-727. 

The other elongation factors, EF-ipy and EF-2, are involved, respectively, in the posthydrolytic exchange of GDP with GTP and in the translocation of peptidyl-tRNA on the ribosome. Of these, EF-2 (95 kDa) has a unique characteristic in the form of a histidine residue at position 715 modified into diphthamide, as a result of which it can be ADP-ribosylated either endogenously or by bacterial toxins such as diphtheria toxin (Riis et al., 1990b). EF-3, which is present in some yeast and fungal species, is a 125 kDa polypetide chain. A unique property of EF-3 is its ability to function with any of the three purine nucleosides (A, G, and I), perhaps to facilitate the interaction of EF-1 a, GTP, and aminoacyl-tRNA. The requirement for EF-3, even in vitro, is an exclusive property of yeast ribosomes. When yeast factors are tested with mammalian ribosomes, EF-3 has no effect (Riis et al., 1990). 

Nilsson L and Nygard O (1986). The mechanism of the protein-synthesis elongation cycle in eukaryotes. Effect of ricin on the ribosomal interaction with elongation factors. Eur J Biochem, 161, 111-117. 

Elongation factors Non-ribosomal protein factors that are necessary participants in the chain-elongation cycle of polypeptide synthesis they interact with the ribosome-mRNA complex or with other major cycle participants. 

Elongation factors, transfer factors proteins catalysing the elongation of peptide chains in Protein biosynthesis (see). Three have been isolated from bacteria EFT, which is a mixed dimer of two proteins, Ts (M, 42,000) and 1 i (M, 44,000), and EFG. Bacterial E. f. do not interact with the SOS ribosomes of eukar-... 

In the protein elongation process the EF-Tu and EF-G cycles themseves interact with the mRNA-pro-gramed ribosome cyclically and since (i) EF-TU has to be released from the ribosome before EF-G can bind to it and vice versa and (ii) GTP hydrolysis is required for the release of both factors, there is a stoichiometric relationship between the number of GTPs hydrolysed and the number of amino acids incorporated into the protein synthesized. This contrasts with the other GTPases, e.g. heterotrimeric G-proteins, Ras proteins, which continue to transmit a signal as long as they remain in the E - GTP form, a key feature of the signal amplification process. 

Mizumoto, K., Iwasaki, K. and Kaziro, Y. (1974) Studies on polypeptide elongation factor 2 from pig liver. III. Interaction with guanine nucleotide in the presence and absence of ribosomes. J. Biochem. 

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