Regulation of Pathways

Hemoglobin Animations

The Structure of Hemoglobin Rearranges Between POOR and GOOD Forms

Select a picture above. These will initially be shown to 'morph' between the POOr and GOOD state. You may select to freeze one state or the other with the buttons below. (These button do nothing when the graph is selected above)

Freeze the structure in the POOR state

Freeze the structure in the GOOD state

morph structures from POOR GOOD

Hemoglobin is the prototypical cooperative protein. It contains 4 subunits: 2 α and 2 β. The α and β subunits bear similar sequences and VERY similar structures. This allows us to speak about hemoglobin as if it contains 4 identical subunits in terms of Cooperativity. Myoglobin, even though it carries the same function (bind oxygen) and bears a very similar structure to a hemoglobin subunit does not display Cooperativity because it is a monomeric protein.
The Solid hyperbolic curve represents the binding of oxygen to myoglobin as [O2] changes. The sigmoidal curve represents oxygen binding to hemoglobin as [O2] changes. There are two dashed vertical lines in the plot that represent the [O2] in the lungs (right most line) and [O2] in the tissues (left most line).
If hemoglobin acted like myoglobin we would suffocate rather quickly!
Furthermore the hemoglobin line is with 2,3 bisphosphoglycerate (2,3BPG) in the blood. With out 2,3 BPG the hemoglobin line shifts left about 40%....

Cooperative binding like that displayed by the sigmoidal curves requires that the protein exhibits two distinct conformations. One with a relatively high KD (labeled 'T' or 'poor' state) and one with a relatively low KD (labeled 'R' or 'Good' state). The two forms exist in a dynamic equilibrium with the the 'T' dominating in the substrate free form. As Substrate concentration increases the 'R' form becomes dominant due to the shifting equilibrium.
What are these structural changes and how does it affect Cooperativity. Select the radio buttons above to see animations of hemoglobin structures in the GOOD and POOR structural forms.

Same thing in Jmol Hemoglobin Structure POOR/GOOD

Three different structures of hemoglobin are superimposed below.

  1. The structure of the POOR form that does not have any oxygen bound at the heme (this structure is displayed when you first begin the program).
  2. The structure of the GOOD form with oxygen bound to the hemes (two red spheres projecting out of the heme plane at an angle).
  3. The structure of the POOR form with 2,3 bisphosphoglycerate bound between the β and δ subunits.

The structures of the POOR and GOOD have an overall similar shape and fold, but differ slightly and in their oxygen binding affinity. In order to highlight the similarities and differences the structures are superimposed so that the heme molecules of the α and β subunits overlap as well as possible.

What To Look For

Between the POOR and GOOD forms there is a small, but significant, change in the heme conformation. In the POOR form the iron is slightly out of the plane of the heme, while in the GOOD form the iron is centered in the plane of the heme. While this appears small it is sufficient to alter the oxygen binding affinity.

What is important is to trace how this change in one subunit is communicated to the neighboring subunits. As the iron atom changes position it alters the angle of the ring of the histidine attached to it. This results in a small motion of helix of which this HIS is part. amino acids at the end of this helix are essential in making contacts with a neighboring subunit. The main changes are observed between the α and δ subunits as well as the β and γ subunits. The interfaces between the α and β subunits as well as between the γ and δ are fairly rigid and do not change much.

Hemoglobin consists of two different types of subunits that are similar in sequence and structure but not identical. An α/β pair has one of each as does a γ/δ pair. The interface between subunits of a pair is far more extensive than the interface between the pairs. For this reason Hemoglobin is frequently described as a dimer of dimers. Look to see how little the structure changes between the α/β and how extensive the change it between the α/δ subunits.

What the Buttons Do

The checkboxes are "features" that you may turn On or Off individually or all at once. The Radio buttons choose which structure(s) to display or compare. The bottom three checkboxes alter the color of a specific structure to make it easy to identify.



Color Coding

α Subunit
β Subunit
γ Subunit
δ Subunit

Messages about the currently highlighted features
Click on an atom to diplay identity here