Allosterism in haemoglobin

Conformations in haemoglobin

Each one of the four globin subunits may alternate between two conformations. This model presents only the states where the 4 subunits are in the same conformation:

• (tense), with low affinity for oxygen.
• (relaxed), with higher affinity for oxygen.

You may also appreciate the differences in the shape of the protein in both states using a model with

between both conformations.

Allosterism and cooperativity should not be confused:

• Allosterism refers to the existence of two conformations the interconversion of which is induced by binding of an allosteric ligand or effector, at a site different from the active site of the protein (in this case, the active site is the haem group; an example of effector is illustrated next).
• Cooperativity refers to the conformation of one subunit affecting the conformation of the other subunits: when one globin subunit has changed from T to R it makes it easier for the other 3 subunits to change to R conformation too.

Allosteric effector for haemoglobin

The ligand 2,3-bisphosphoglycerate is an example of allosterism, since it easily binds the T conformation, but not the R. Consequently, high intracellular concentrations of 2,3-BPG shift the equilibrium towards the T form and, hence, favour the release of oxygen.

Let's examine the structures to see which is the reason for this binding preference to the T form:

BPG binds at a pocket between the 4 globin subunits; this space is present in the T form and interaction between BPG and several groups of the protein is allowed, which stabilises this T form. On the contrary, in the R conformation the pocket closes up and there is no space fo fit the BPG molecule (note that in the model BPG would clash with the atoms from the protein, here displayed as a semitransparent surface).