As scientists have learned more of the details of cell biology, they have recognized an increasing degree of sophistication in cell chemistry. Thus, not only do we now know that protein machines play a predominant role, but it has also become clear that they are very often localized to specific sites in the cell, being assembled and activated only where and when they are needed. As one example, when extracellular signaling molecules bind to receptor proteins in the plasma membrane, the activated receptors often recruit a set of other proteins to the inside surface of the plasma membrane to form a large protein complex that passes the signal on (discussed in Chapter 15).
The mechanisms frequently involve scaffold proteins. These are proteins with binding sites for multiple other proteins, and they serve both to link together specific sets of interacting proteins and to position them at specific locations inside a cell. At one extreme are rigid scaffolds, such as the cullin in SCF ubiquitin ligase (see Figure 3–71). At the other extreme are the large, flexible scaffold proteins that often underlie regions of specialized plasma membrane. These include the
Figure 3–77 How “protein machines” carry out complex functions.
These machines are made of individual proteins that collaborate to perform a specific task (Movie 3.13). The movement of these proteins is often coordinated by the hydrolysis of a bound nucleotide such as ATP or GTP. Directional allosteric conformational changes of proteins that are driven in this way often occur in a large protein assembly in which the activities of several different protein molecules are coordinated by such movements within the complex.
Discs-large protein (Dlg), a protein of about 900 amino acids that is concentrated in special regions beneath the plasma membrane in epithelial cells and at synapses. Dlg contains binding sites for at least seven other proteins, interspersed with regions of more flexible polypeptide chain. An ancient protein, conserved in organisms as diverse as sponges, worms, flies, and humans, Dlg derives its name from the mutant phenotype of the organism in which it was first discovered; the cells in the imaginal discs of a Drosophila embryo with a mutation in the Dlg gene fail to stop proliferating when they should, and they produce unusually large discs whose epithelial cells can form tumors.
Although incompletely studied, Dlg and a large number of similar scaffold proteins are thought to function like the protein that is schematically illustrated in Figure 3–78. By binding a specific set of interacting proteins, these scaffolds can enhance the rate of critical reactions, while also confining them to the particular region of the cell that contains the scaffold. For similar reasons, cells also make extensive use of scaffold RNA molecules, as discussed in Chapter 7.
Many Proteins Are Controlled by Covalent Modifications That Direct Them to Specific Sites Inside the Cell
We have thus far described only a few ways in which proteins are post-translationally modified. A large number of other such modifications also occur, more than 200 distinct types being known. To give a sense of the variety, Table 3–3 presents
Figure  3–78 How the proximity created by scaffold proteins can greatly speed reactions in a cell. In this example, long unstructured regions of polypeptide chain in a large scaffold protein connect a series of structured domains that bind a set of reacting proteins. The unstructured regions serve as flexible “tethers” that greatly speed reaction rates by causing a rapid, random collision of all of the proteins that are bound to the scaffold. (For specific examples of protein tethering, see Figure 3–54 and Figure 16–18; for scaffold RNA molecules, see Figure 7–49B.) a few of the modifying groups with known regulatory roles. As in phosphate and ubiquitin additions described previously, these groups are added and then removed from proteins according to the needs of the cell.