Protein Synthesis: Elongation, Termination, and Regulation
Protein Synthesis Stages
22) Translation Elongation: The nascent polypeptide chain is extended by the covalent bonding of successive amino acid units. Each amino acid is carried to the ribosome by its tRNA, which is positioned correctly to match the corresponding codon in mRNA. Elongation requires cytosolic proteins called elongation factors, and the binding is powered by the hydrolysis of GTP.
23) Termination and Release: Polypeptide chain termination is signaled by a stop codon in the mRNA. The polypeptide chain is released from the ribosome with the help of proteins called release factors.
24) Folding and Post-Translational Modification: To become biologically active, the new polypeptide must fold into its correct three-dimensional conformation. Before or after folding, the polypeptide may undergo enzymatic modifications, including the removal of signal sequences (15 to 30 amino acid residues) that direct the protein to its final destination in the cell. Specific hydroxyl groups of Serine, Threonine, and Tyrosine can be enzymatically phosphorylated by adding phosphate groups from ATP. The formation of disulfide bonds helps protect the protein’s conformation against denaturation in the extracellular medium.
25) tRNA: Transfer RNA molecules are relatively small, single-stranded RNA molecules that fold into a cloverleaf structure with four arms. Cells possess at least one type of tRNA for each amino acid. The amino acid arm carries a specific amino acid esterified by its carboxyl group. The anticodon arm contains the anticodon (a sequence of three bases complementary to the codon in mRNA, which specifies the amino acid). The other two major arms are involved in the folded tRNA structure.
Inhibitors and Regulation
27) Inhibitors of Protein Synthesis: Protein synthesis is a central function in cellular physiology and a major target of many antibiotics and natural toxins. With some exceptions, these antibiotics inhibit bacterial protein synthesis. Antibiotics are valuable tools for studying protein synthesis because they can inhibit specific steps. For example, puromycin, produced by a fungus, is a known inhibitor with a structure similar to aminoacyl-tRNA, allowing it to bind to the ribosome and inhibit protein synthesis. Chloramphenicol inhibits protein synthesis in bacteria, mitochondria, and chloroplasts.
28) Principles of Genetic Regulation: Some genes, such as those encoding enzymes in metabolic pathways, are expressed at a relatively constant level in virtually all cells; these are called housekeeping genes. The cellular levels of other gene products increase or decrease in response to molecular signals. These regulated genes are either inducible or repressible. Inducible genes increase their expression in response to specific molecular signals, a process called induction. Repressible genes decrease their expression in response to a molecular signal, a process called repression.
29) Levels of Regulation: Positive and Negative: At least three types of proteins regulate the initiation of transcription:
- Specific factors that modify the specificity of RNA polymerase.
- Repressors that prevent RNA polymerase from accessing the promoter.
- Activators that enhance the interaction of RNA polymerase with the promoter.