Translation amino acid activation

AMINO ACID ACTIVATION AND CODON TRANSLATION BY tRNAs... 

Like amino acid activation (see p. 248), protein biosynthesis (translation) takes piace in the cytopiasm. it is cataiyzed by compiex nucieoprotein particies, the ribosomes, and mainiy requires GTP to cover its energy requirements. 

Figure 10.4. Sequences of ORF nucleotide and protein translate. The sequences for nucleotides and translated amino acids from Frame +3 ORF of proopiomelanocortin DNA (Figure 10.3) are displayed by clicking SixFrame button and then activating the desired frame bar. The initiation codon (sky) and stop codon (pink) suggests potential start and end positions of CDS/translate(s) for the Frame.

Among activated forms of amino acids, mixed anhydrides with inorganic phosphate or phosphate esters require a special discussion because they are universally involved in peptide biosynthesis through the ribosomal and non-ribosomal pathways. These mixed anhydrides have stimulated studies in prebiotic chemistry very early in the history of this field. Amino acyl adenylates 18c have been shown to polymerize in solution [159,160] and in the presence of clays [139]. However, their participation as major activated amino acid species to the prebiotic formation of peptides from amino acids is unlikely for at least two reasons. Firstly, amino acid adenylates that have a significant lifetime in aqueous solution become very unstable as soon as either CO2 or bicarbonate is present at millimolar concentration [137]. Lacey and coworkers [161] were therefore conduced to consider that CO2 was absent in the primitive atmosphere for aminoacyl adenylate to have a sufficient lifetime and then to allow for the emergence of the modern process of amino acid activation and of the translation apparatus. But this proposition is unlikely, as shown by the analysis of geological records in favor of CO2 contents in the atmosphere higher than present levels [128]. It is also in contradiction with most studies of the evolution of the atmosphere of telluric planets [30,32], Secondly, there is no prebiotic pathway available for adenylate formation and ATP proved to be inefficient in this reaction [162]. 

The second major step of gene expression involves the translation of a protein, e.g., enzymes, structural proteins, secreted proteins, gene expression factors, etc., in which the mRNA interacts with ribosomes and amino acid activated transfer RNA to direet the synthesis of the protein coded for by the mRNA sequence. 

Amino-acid activation is the first stage of the cell s translating mechanism (Novelli, 1967). 

Transfer RNA (tRNA) plays a key role in the translation Transfer RNA process in the amino acid activation reaction... 

In translating the message contained in m-RNA into protein, specific amino acids are recognised, assembled and joined together in the sequence specified by the m-RNA. The amino acids do not, however, enter directly into the system but are first activated in reactions involving ATP and amino acid activating enzymes (AAA enzymes) a separate specific enzyme for each of the 20 individual protein amino acids ... 

In the experiments for which results are shown in Figure 3B, in order to rescue the expression of CBP, we also constmcted a version of CBP mRNA that was not cleavable (nc) by the active CBP-ribozyme (CBP C in which the triplet at the cleavage site was changed from the cleavable GUC to the uncleavable GCC, a mutation that does not change the translated amino acids). As expected, stable introduction of CBP c mRNA completely restored the production of CBP in F9 cells that expressed an active CBP-ribozyme. 

The protein folding problem is the task of understanding and predicting how the information coded in the amino acid sequence of proteins at the time of their formation translates into the 3-dimensional structure of the biologically active protein. A thorough recent survey of the problems involved from a mathematical point of view is given by Neumaier [22]. 

Endothelin. The endothelin (ET) peptide family (50) comprises thiee peptides ET-1 (133), ET-2 (134), and ET-3 (135). ET-1, the most abundant, is a 21-amino acid peptide. A 203-amino acid peptide piecuisoi, piepioET, is cleaved after translation by endopeptidases to form a 38-amino acid proET which is converted to active ET by a putative endothelin-converting enzyme (ECE). ET-3 differs from ET-1 and ET-2 by sis amino acids. 

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. 

The classical cadherins are translated as precursor because they are N-terminally cleaved to reveal the mature proteins. This processing is required to activate the cell adhesion function of cadherins. Cadherins interact in trans (i.e., from opposite cells) via the most N-terminal cadherin rqDeats. A short amino acid sequence within this repeat, histidine-alanine-valine (HAV), has been implicated in mediating cell-cell contacts as HAV peptides can disrupt cadherin-dependent cell adhesion. Besides the trans-interactions of cadherins, the extracellular domains are also capable of forming cis-dimers through lateral amino acid contacts between cadherin molecules on one cell. This dimerization again mainly involves the first cadherin repeat. A zipper model based on the pattern of alternating cis- and trans-dimers [1] for the adhesive interactions has been proposed. 

Increased protein synthesis Increased amino acid uptake/increased translation of mRNA Akt-mediated stimulation of system A amino acid transporter and stimulation of mRNA-translation through activation of p70S6kinase and elongation initiation factor 4 (elF4). Possible involvement of atypical PKCs... 

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