The functional unit of Hemoglobin is a tetramer. Each monomer contains a heme group that has the capacity to bind a molecule of oxygen. Thus functional hemoglobin can bind four molecules of oxygen. Oxygen binding to hemoglobin exhibits cooperativity. The first molecule of oxygen that binds a subunit of hemoglobin makes it easier for the second molecule of oxygen to bind (another subunit), which in turn makes it easier for the third molecule to bind, and so on.

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Structural Changes that Accompany Oxygen Binding to Hemoglobin

In this structure the four individual hemoglobin subunits are depicted as ribbon diagrams and colored individually to show the quaternary structure of the protein. The heme groups are depicted using bonds. The four heme groups are far apart from each other. How does the binding of an oxygen molecule to one heme group influence the binding of an oxygen molecule to a different heme group? Given that the heme groups are far apart from each other, 'communication' between the groups must be mediated by changes in protein structure that occur upon oxygen binding. What structural changes occur upon oxygen binding?

Since oxygen binds at the heme group, the heme group as well as amino acids that interact with the heme group must play an important role in the conformational changes that lead to cooperativity. Lets look at the oxygen free (deoxy) and oxygen bound (oxy) forms of hemoglobin to understand the structural changes that occur upon oxygen binding.

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2. The Fe atom (brown) at the center of the heme group has six coordination sites, four of which are occupied by nitrogens (blue) from the porphyrin ring.

3. One of these sites is occupied by the nitrogen from the sidechain of a His residue (residue 8 on the F helix). This residue is termed the proximal His. The remaining coordination site remains free to bind oxygen.

4. Notice that the Fe atom in the heme group lies slightly away from the plane of the porphyrin ring, towards to proximal His residue.

5. This movement of the Fe atom caused the proximal HIs to move with it, in turn causing the F helix of the subunit to move. This conformation change results in a change within the subunit interface that makes it easier for the next oxygen molecule to bind the second heme group.

6. You can view the changes at the heme group, and the proximal His, in the deoxy and oxy hemoglobins as an animation. This animation cycles between the oxygen free and oxygen bound forms of hemoglobin and shows the movement of the Fe atom into the plane of the porphyrin ring upon oxygen binding. You can also see the resulting movement of the proximal His and the F helix.