Concepts Summary
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George Beadle and Edward Tatum developed the one gene, one enzyme hypothesis, which proposed that each gene specifies one enzyme; this hypothesis was later modified to become the one gene, one polypeptide hypothesis.
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Proteins are composed of twenty different amino acids. The amino acids in a protein are linked together by peptide bonds. Chains of amino acids fold and associate to produce the secondary, tertiary, and quaternary structures of proteins.
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Solving the genetic code required several different approaches including the use of synthetic mRNAs with random sequences and short mRNAs that bind charged tRNAs.
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The genetic code is a triplet code: three nucleotides specify a single amino acid. It is also degenerate (meaning that more than one codon may specify an amino acid), nonoverlapping, and universal (almost).
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Different tRNAs (isoaccepting tRNAs) may accept the same amino acid. Different codons may pair with the same anticodon through wobble, which can exist at the third position of the codon and allows some nonstandard pairing of bases in this position.
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The reading frame is set by the initiation codon. The end of the protein-coding section of an mRNA is marked by one of three termination codons.
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Protein synthesis comprises four steps: (1) the binding of amino acids to the appropriate tRNAs, (2) initiation, (3) elongation, and (4) termination.
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The binding of an amino acid to a tRNA requires the presence of a specific aminoacyl-tRNA synthetase and ATP. The amino acid is attached by its carboxyl end to the 3′ end of the tRNA.
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In bacterial translation initiation, the small subunit of the ribosome attaches to the mRNA and is positioned over the initiation codon. It is joined by the first tRNA and its associated amino acid (N-formylmethionine in bacterial cells) and, later, by the large subunit of the ribosome. Initiation requires several initiation factors and GTP.
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In elongation, a charged tRNA enters the A site of a ribosome, a peptide bond is formed between amino acids in the A and P sites, and the ribosome moves (translocates) along the mRNA to the next codon. Elongation requires several elongation factors and GTP.
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Translation is terminated when the ribosome encounters one of the three termination codons. Release factors and GTP are required to bring about termination.
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Each mRNA may be simultaneously translated by several ribosomes, producing a structure called a polyribosome.
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Cells possess RNA surveillance mechanisms that eliminate mRNAs with errors that may create problems in translation.
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Antibiotics frequently work by interfering with translation, because many aspects of translation differ in bacteria and eukaryotes.
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Many proteins undergo posttranslational modification.