Protein synthesis is the culmination of the transfer of genetic information from DNA to proteins. In this transfer, information must be translated from the four-nucleotide-language of DNA and RNA to the twenty-amino acids-language of proteins. The genetic code, in which three nucleotides in mRNA (codon) specify an amino acid, represents the translation dictionary of the two languages. The tRNA molecule is the bridge between these two languages. The tRNA accomplishes this task by virtue of its anticodon loop which interacts with specific codons on the mRNA, and amino acids via its amino acid attachment site located on the 3' end of the molecule. The process of translation consists of three parts; initiation, elongation, and termination. Initiation involves the assembly of the ribosome and charged tRNA at the initiation codon (AUG) of the mRNA. This assembly process is mediated by initiation factors and requires the expenditure of energy in the form of GTP. Elongation is a stepwise addition of individual amino acids to a growing peptide chain by the action of peptidyl transferase. The charged tRNA molecules are brought to the ribosome by elongation factors at the expense of GTP hydrolysis. Termination of protein synthesis occurs when the ribosome reaches a stop codon and releasing factors catalyze the release of a protein. After release, the newly synthesized protein must be correctly folded with the help of ancillary proteins called chaperones. Many newly synthesized proteins must also be modified, by a variety of chemical and structural changes, before they are biologically active. Once a protein is no longer needed, it is degraded in an equally complex, macromolecular complex called the proteasome.
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- Review the mechanism of action of various drugs that inhibit protein synthesis on the bacterial ribosome.
- Compare and contrast mechanisms that assure the fidelity of DNA and protein synthesis.
- Describe the signal sequences that target proteins to the lysosome.
- Discuss the role of the N-terminal amino acid as a factor regulating the rate of turnover of a cytoplasmic protein.
- Explain how viruses take control of the cellular protein translation machinery during viral infections to favor the synthesis of viral proteins.
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Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN, Cate JH, Noller HF. Crystal structure of the ribosome at 5.5 A resolution. Science 2001;292:883-896, 2001.
Full article
|
Giasson BI, Lee VM-Y. Are Ubiquitination pathways central to Parkinson's disease? Cell 2003;114:1-8.
Full article
|
Gilbert DN, Dworkin RJ, Raber SR, Leggett JE. Outpatient parenteral antimicrobial drug therapy. N Engl J Med 1997;337:829-838.
Full article
|
Hartl FU, Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 2002;295:1852-1858.
Full article
|
Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J Med 1997;336:708-716.
Full article
|
Siegel V. A second signal recognition event required for translocation into the endoplasmic reticulum. Cell 1995;82:167-170.
Full article
|
Steitz TA, Moore PB. RNA, the first macromolecular catalyst: the ribosome is a ribozyme. Trends Biochem Sci 2003;28:411-418.
Full article
|
Zheng N, Gierasch L. Signal sequences: the same yet different. Cell 1996;86:849-852.
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