Chapter 8: Protein Synthesis, Processing, and Regulation
Chapter Summary
TRANSLATION OF mRNA
Transfer RNAs: Transfer RNAs serve as adaptors that align amino acids on the mRNA template. Aminoacyl tRNA synthetases attach amino acids to the appropriate tRNAs, which then bind to mRNA codons by complementary base pairing.
The Ribosome: Ribosomes consist of two subunits, which are composed of proteins and ribosomal RNAs. The 23S rRNA is the primary catalyst of peptide bond formation.
The Organization of mRNAs and the Initiation of Translation: Translation of both prokaryotic and eukaryotic mRNAs initiates with a methionine residue. In bacteria, initiation codons are preceded by a sequence that aligns the mRNA on the ribosome by base pairing with 16S rRNA. In eukaryotes, most initiation codons are identified by scanning from the 5' end of the mRNA, which is recognized by its 7-methylguanosine cap.
The Process of Translation: Translation is initiated by the binding of methionyl tRNA and mRNA to the small ribosomal subunit. The large ribosomal subunit then joins the complex, and the polypeptide chain elongates until the ribosome reaches a termination codon in the mRNA. A variety of nonribosomal factors are required for initiation, elongation, and termination of translation in both prokaryotic and eukaryotic cells.
Regulation of Translation: Translation of specific mRNAs can be regulated by the binding of repressor proteins and by proteins that localize mRNAs to specific regions of cells. Controlled polyadenylation of mRNA is also an important mechanism for the regulation of translation during early development. In addition, the translation of many mRNAs may be controlled by noncoding microRNAs that either repress translation or target homologous mRNAs for degradation. Finally, the general translational activity of cells can be regulated by modification of initiation factors.
PROTEIN FOLDING AND PROCESSING
Chaperones and Protein Folding: Molecular chaperones facilitate protein folding by binding to and stabilizing unfolded or partially folded polypeptide chains.
Enzymes that Catalyze Protein Folding: At least two types of enzymes, protein disulfide isomerase and peptidyl prolyl isomerase, catalyze protein folding.
Protein Cleavage: Proteolysis is an important step in the processing of many proteins. For example, secreted proteins and proteins incorporated into most eukaryotic organelles are targeted to their destinations by amino-terminal sequences that are removed by proteolytic cleavage as the polypeptide chain crosses the membrane.
Glycosylation: Many eukaryotic proteins, particularly secreted and plasma membrane proteins, are modified by the addition of carbohydrates in the endoplasmic reticulum and Golgi apparatus.
Attachment of Lipids: Covalently attached lipids frequently target and anchor proteins to the plasma membrane.
REGULATION OF PROTEIN FUNCTION
Regulation by Small Molecules: Many proteins are regulated by the binding of small molecules, such as amino acids and nucleotides, which induce changes in protein conformation and activity.
Protein Phosphorylation: Reversible phosphorylation, which controls the activities of a wide variety of cellular proteins, results from the action of protein kinases and phosphatases. Other modifications, such as nitrosylation, also regulate the activities of some proteins.
Protein-Protein Interactions: Interactions between polypeptide chains are important in the regulation of allosteric enzymes and other cellular proteins.
PROTEIN DEGRADATION
The Ubiquitin-Proteasome Pathway: The major pathway of selective protein degradation in eukaryotic cells uses ubiquitin as a marker that targets proteins for rapid proteolysis by the proteasome.
Lysosomal Proteolysis: Lysosomal proteases degrade extracellular proteins taken up by endocytosis and are responsible for the degradation of cytoplasmic organelles and long-lived cytosolic proteins. Autophagy is activated as a response to cell starvation.
