Cooperative Allosteric Transitions

Many proteins have multiple subunits, where each subunit contains a separate ligand binding site.

When a molecule, known as a modulator, binds to one of the subunits it triggers a conformational change in the binding sites of the other subunits changing their affinity for their respective ligands. This is called a cooperative allosteric transition and can be explained by several theoretical models.

The concerted or “all-or-none” model assumes that all of the subunits exist together in either an “off” or “on” conformation.

Binding can occur in either form, however, the “on” state has a higher affinity for the ligand than the “off” state. When a ligand binds at any of the subunits, it promotes the simultaneous transformation of all of the binding sites to the high-affinity form.

Cooperativity can also be explained by the sequential model, which assumes that each subunit can exist independently in a high or low-affinity state, but is more likely to be in the high-affinity state when the ligand is bound to any of the subunits. 

The binding sites of allosteric proteins are usually a mix of flexible and fixed segments of the amino acid chain. When a ligand binds, these unstable parts are stabilized in a particular conformation, and this affects the shape of the binding sites on the other subunits. 

Hemoglobin is an example of a tetrameric protein that undergoes a cooperative allosteric transition when oxygen binds.

Each subunit of hemoglobin has a single binding site. When one molecule of oxygen binds to a single subunit, cooperativity increases the affinity for oxygen on the remaining binding sites making it easier for oxygen to bind to a molecule of hemoglobin that already has oxygen bound to it.