5e Chapter29 2003

5e Chapter29 2003 - 2002 2003 by Changwon Kang Chapter 29...

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© 2002, 2003 by Changwon Kang Chapter 29 1 Chapter 29: Protein Synthesis A. Translation: Four-letter alphabet language (nucleotide sequence) of mRNA is translated into twenty-letter language (amino acid sequence) of protein. Transfer RNAs (tRNAs) are the dictionary for translation. They have two functional parts. The anticodon loop reads nucleotide sequence of mRNA, and the CCA terminus dictates the amino acid sequence. Ribosome catalyzes translation. It is a ribozyme, as rRNAs play catalytic and other functional roles. Ribosomal proteins play little. Chemically, proteins are polymers of amino acids. They are biochemically synthesized by polymerization of aminoacyl-tRNAs. Protein is synthesized in the N-to-C direction, as messenger RNA (mRNA) is translated in the 5'-to-3' direction. The amino group of aminoacyl-tRNA attacks the C-terminal carbonyl group of chain to form a peptide bond. A free tRNA is released. With error rate of ~10 4 , proteins of 1,000 amino acids are synthesized correctly 90% of time. Conversion of 4-alphabet system to 20-alphabet system is not straightforward. Sixteen (4 2 ) words of 2 letters are just short for the 20 words necessary in protein. Sixty-four (4 3 ) words of 3 letters are too many, so amino acids except Met and Trp are coded by multiple triplet codons. B. Aminoacyl-tRNAs (1) Amino acids are activated by tRNAs for polymerization. When amino acids are directly polymerized, a new bond should be generated using energy. When aminoacyl-tRNAs are polymerized, an ester bond is replaced by a peptide bond. (All mechanisms of biochemical polymerizations do not use free unit residues directly, but use their activated forms as substrates.) Specific aminoacyl-tRNA synthetases activate amino acids first to aminoacyl- adenylates using ATP and replace the AMP of each aminoacyl-AMP by a specific tRNA. The product pp i is hydrolyzed, driving the reaction forward. The 3'-end residue of tRNA is also AMP. Linkage is different. The carboxyl group of an amino acid is linked to 5'-P of AMP in aminoacyl-AMP, but to the 2'- or 3'-OH of the 3'-terminal AMP of tRNA in aminoacyl-tRNA. Activated forms are amino acid esters. (2) Specificity Aminoacyl-tRNA synthetases implement the genetic code, and each of them is highly specific for a given amino acid (error rate is 10 5 or 10 4 ). Only they know the code. Cells usually have 20 kinds of them, one for each amino acid. The activation site of every synthetase discriminates against non-cognate amino acids. Except a few, they have an editing site as well. For example, the Thr-tRNA synthetase activation site discriminates against all amino acids except for Thr and Ser, producing Thr-tRNA Thr (correct) and Ser-tRNA Thr (wrong). Then, only Ser-tRNA Thr binds to the editing site and is cleaved. Each enzyme recognizes its cognate tRNAs (usually more than one kind) primarily on the basis
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5e Chapter29 2003 - 2002 2003 by Changwon Kang Chapter 29...

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