Hemoglobin Allostery

Hemoglobin is the oxygen carrier in the blood. Hemoglobin is a protein made up of four chains - two alpha and two beta chains. The arrangement of the chains is such that hemoglobin may be viewed as a dimer of dimers, each dimer being made up of one alpha and one beta chain (Figure 1). Each one of the chains carries a non-covalently bound heme group that binds oxygen. The heme group is a macrocyclic molecule - called a porphyrin - which has a bound iron atom (Figure 2).
[Ribbon Diagram of Hemoglobin]
Figure 1.The Hemoglobin tetramer. Alpha Chains are in red and beta chains in green.
[Ball and Stick Picture of Porphyrin]
Figure 2.The Heme group. Carbon atoms are colored white, oxygens in red, nitrogens in blue and iron golden.

Each heme group can bind one oxygen molecule. Thus, the hemoglobin tetramer can bind a total of four oxygen molecules. Hemoglobin also serves the purpose of transporting carbon dioxide. Oxygen is bound by hemoglobin at the lungs, carried through the blood stream to various tissues, where it gives up the oxygen, and binds carbon dioxide and transports it back to the lungs. Carbon dioxide is bound as the bicarbonate ion, HCO3-, at the dimer interface and not to the heme.

The binding of oxygen to hemoglobin is cooperative. Thus, binding of one oxygen causes the next oxygen to bind more strongly, the third oxygen even more strongly and so on. In fact, hemoglobin is usually observed in only two states - all four chains carrying oxygen, or completely oxygen free. This is shown by the oxygen binding curve in figure 3.

[Oxygen Binding Curves for Hemoglobin and 
Figure 3. Oxygen binding curves for myoglobin and hemoglobin.

In contrast to myoglobin, the single chain oxygen storage molecule found in tissues, which displays normal saturation binding of oxygen, the curve for hemoglobin is sigmoidal, indicating cooperative binding. The modulation of the affinity of a site for a ligand by ligand binding at another site is called Allostery.

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