Figure 6–86 Two general ways of inducing the degradation of a specific protein. (A) Activation of a specific E3 molecule creates a new ubiquitin ligase. Eukaryotic cells have many different E3 molecules, each activated by a different signal. (B) Creation of an exposed degradation signal in the protein to be degraded. This signal binds a ubiquitin ligase, causing the addition of a polyubiquitin chain to a nearby lysine on the target protein. All six pathways shown are known to be used by cells to induce the movement of selected proteins into the proteasome.
which directs the ubiquitylation of the protein and sends it to the proteasome for degradation. Thus, the majority of human proteins carry their own signals for destruction. It has been proposed that when a protein is properly folded (and, before that, when it is in contact with a chaperone), this acetylated N-terminus is buried and therefore inaccessible to the E3 enzyme. According to this idea, as a protein ages and becomes damaged (or if it fails to fold correctly from the start), this destruction signal becomes exposed, and the protein is destroyed.
There Are Many Steps From DNA to Protein
We have seen so far in this chapter that many different types of chemical reactions are required to produce a properly folded protein from the information contained in a gene (Figure 6–87). The final level of a properly folded protein in a cell therefore depends upon the efficiency with which each of the many steps is performed. We also now know that the cell devotes enormous resources to selectively degrading proteins, particularly those that fail to fold properly or accumulate damage as they age. It is the balance between the rates of synthesis and degradation that determines the final amount of every protein in the cell.
In the following chapter, we shall see that cells have the ability to change the levels of their proteins according to their needs. In principle, any or all of the steps in Figure 6–87 could be regulated for each individual protein. As we shall see in Chapter 7, there are examples of regulation at each step from gene to protein.
5˜3˜DNA introns exons INITIATION OF TRANSCRIPTION CLEAVAGE, POLYADENYLATION, AND TERMINATION EXPORT CAPPING, ELONGATION SPLICING AAAA mRNA NUCLEUS CYTOSOL cap poly-A tail
Figure 6–87 The production of a protein by a eukaryotic cell. The final level of each protein in a eukaryotic cell depends upon the efficiency of each step depicted.
The translation of the nucleotide sequence of an mRNA molecule into protein takes place in the cytosol on a large ribonucleoprotein assembly called a ribosome. Each amino acid used for protein synthesis is first attached to a tRNA molecule that recognizes, by complementary base-pair interactions, a particular set of three nucleotides (codons) in the mRNA. As an mRNA is threaded through a ribosome, its sequence of nucleotides is then read from one end to the other in sets of three according to the genetic code.