Figure 3–60 a cooperative allosteric transition in an enzyme composed of two identical subunits. This diagram illustrates how the conformation of one subunit can influence that of its neighbor. The binding of a single molecule of an inhibitory ligand (yellow) to one subunit of the enzyme occurs with difficulty because it changes the conformation of this subunit and thereby disrupts the symmetry of the enzyme. Once this conformational change has occurred, however, the energy gained by restoring the symmetric pairing interaction between the two subunits makes it especially easy for the second subunit to bind the inhibitory ligand and undergo the same conformational change. Because the binding of the first molecule of ligand increases the affinity with which the other subunit binds the same ligand, the response of the enzyme to changes in the concentration of the ligand is much steeper than the response of an enzyme with only one subunit (see Figure 3–59 and Movie 3.10).
Figure 3–59 enzyme activity versus the concentration of inhibitory ligand for single-subunit and multisubunit allosteric enzymes. For an enzyme with a single subunit (red line), a drop from 90% enzyme activity to 10% activity (indicated by the two dots on the curve) requires a 100-fold increase in the concentration of inhibitor. The enzyme activity is calculated from the simple equilibrium relationship  K = [IP]/[I][P], where P is active protein,  I is inhibitor, and IP is the inactive protein bound to inhibitor. An identical curve applies to any simple binding interaction between two molecules, A and B. In contrast, a multisubunit allosteric enzyme can respond in a switchlike manner to a change in ligand concentration: the steep response is caused by a cooperative binding of the ligand molecules, as explained in Figure 3–60. Here, the green line represents the idealized result expected for the cooperative binding of two inhibitory ligand molecules to an allosteric enzyme with two subunits, and the blue line shows the idealized response of an enzyme with four subunits. As indicated by the two dots on each of these curves, the more complex enzymes drop from 90% to 10% activity over a much narrower range of inhibitor concentration than does the enzyme composed of a single subunit.
protein’s activity. When a second enzyme removes the phosphate group, the protein returns to its original conformation and restores its initial activity.
Second, an attached phosphate group can form part of a structure that the binding sites of other proteins recognize. As previously discussed, the SH2 domain binds to a short peptide sequence containing a phosphorylated tyrosine side chain (see Figure 3–40B). More than ten other common domains provide binding sites for attaching their protein to phosphorylated peptides in other protein molecules, each recognizing a phosphorylated amino acid side chain in a different protein context. Third, the addition of a phosphate group can mask a binding site that otherwise holds two proteins together, and thereby disrupt protein–protein interactions. As a result, protein phosphorylation and dephosphorylation very often drive the regulated assembly and disassembly of protein complexes (see, for example, Figure 15–11).
Reversible protein phosphorylation controls the activity, structure, and cellular localization of both enzymes and many other types of proteins in eukaryotic cells. In fact, this regulation is so extensive that more than one-third of the 10,000 or so proteins in a typical mammalian cell are thought to be phosphorylated at any given time—many with more than one phosphate. As might be expected, the addition and removal of phosphate groups from specific proteins often occur in response to signals that specify some change in a cell’s state. For example, the complicated series of events that takes place as a eukaryotic cell divides is largely timed in this way (discussed in Chapter 17), and many of the signals mediating cell–cell interactions are relayed from the plasma membrane to the nucleus by a cascade of protein phosphorylation events (discussed in Chapter 15).