The glucose carrier is able to bind a ligand—the glucose molecule—in either of its low-energy conformations. In contrast, the lac repressor (page 113) can only bind its ligand, the operator region of the lac operon, in one conformation. On its own the protein predominantly adopts this conformation so transcription is prevented as it binds to the DNA. When the lac repressor binds allolactose (a signal that lactose is abundant), it is locked into a second, inactive form that cannot bind to the DNA (Fig. 6.8 on page 113). Transcription is no longer repressed, although the cAMP-CAP complex is additionally required if transcription is to proceed at a high rate. This type of interaction, in which the binding of a ligand at one place affects the ability of the protein to bind another ligand at another location, is called allosteric and is usually a property of proteins with a quaternary structure (i.e., with multiple subunits).
Hemoglobin (Fig. 9.20 on page 205) is an example of a protein where allosteric effects play an important role. Each heme prosthetic group, one on each of the four subunits, can bind an oxygen molecule. We can get an idea of what one subunit on its own can do by looking at myoglobin (Fig. 11.2a), a related molecule that moves oxygen within the cytoplasm. Myoglobin has just one polypeptide chain and one heme. The green line in Figure 11.2b shows the oxygen-binding curve for myoglobin. Starting from zero oxygen, the first small increase in oxygen concentration produces a large amount of binding to myoglobin; the
next increase in oxygen produces a slightly smaller amount of binding, and so on, until myoglobin is fully loaded with oxygen. A curve of this shape is known as hyperbolic. The black line in Figure 11.2b shows the oxygen-binding curve for hemoglobin. Starting from zero oxygen, the first small increase in oxygen concentration produces hardly any binding to hemoglobin. The next increase in oxygen produces much more binding so the curve gets steeper before leveling off again as the hemoglobin becomes fully loaded. This behavior is called cooperative. The explanation for this behavior is that the hemoglobin subunits can exist in one of two states, only one of which has a high affinity for oxygen. The way that the four subunits fit together means that they all must be in one form or the other. When oxygen concentration is low, most of the hemoglobin molecules have their subunits in the low-affinity form. As oxygen increases, it begins to bind to the hemoglobin—little at first as most of the hemoglobin is in the low-affinity form and only a little in the high-affinity form. As oxygen binds, more molecules switch to the high-affinity form as the low- and high-affinity forms are in equilibrium. Eventually virtually all of the molecules have made the switch to the high-affinity form. This produces the curve shown in Figure 11.2b. This cooperative oxygen binding makes hemoglobin an effective transporter as it will load up with oxygen in the lungs but will release it readily in the capillaries of the tissues where the oxygen concentration is low. Myoglobin would release little of its bound oxygen at the oxygen concentrations typical of respiring tissues.
Some enzymes show cooperative behavior caused by an allosteric effect that causes binding of one substrate molecule to make it easier for the other substrate to bind. The degree of cooperativity can be altered by the binding of other molecules (called effectors) that act to switch the enzyme on or off.
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