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.
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.
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
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.