How co-operativity enables ligand affinity to be readily changed. Illustrate your answer by referencing the binding of oxygen to myoglobin and haemoglobin.
Co-operative binding is a type of allosteric behaviour that means the affinity of a protein for its ligand changes as ligand binding occurs (Nelson & Cox, 2008). Co-operative binding can only take place on proteins that have more than one binding site for a ligand and can be positive, meaning affinity for the ligand increases as more ligands are bound, or negative meaning that the biding of one ligand inhibits the binding of subsequent ligands. A good example of the difference between co-operative and non-co-operative binding is the binding of oxygen to myoglobin and haemoglobin. Myoglobin and haemoglobin both contain haem, the molecule to which oxygen binds. Myoglobin is a monomeric, and so has only one haem available for oxygen binding and so cannot participate in co-operative binding. Myoglobin’s function in the body is to store oxygen for use when oxygen levels are very low and its high affinity for oxygen means it can bind oxygen at low saturation and will not give up this oxygen except in times of need, such as during intense exercise (Ahern &Rajagopal, 2012). Haemoglobin however has a different function, to bind oxygen in areas of high saturation and release it in areas of low concentration. This function is made possible by haemoglobin exhibiting positive co-operative binding. Unlike myoglobin, haemoglobin has four subunits; each containing a haem molecule and so can bind a total of four oxygen molecules. The affinity of each subsequent subunit increases as each binding occurs as when oxygen binds to the haem in a subunit, the Fe in the centre of the haem is lifted fractionally which in turn lifts the connected histidine and successive amino acids. This fractional movement causes a conformational change in the subunit which makes the adjacent subunit more favourable to binding oxygen. This conformational change stabilises the R-state, the relaxed state, of haemoglobin where the haemoglobin has an increases affinity for oxygen. When no oxygen binding has occurred the haemoglobin is in the T-state, or tense state, where affinity for oxygen is low. This is more clearly illustrated by an oxygen-haemoglobin saturation curve, see figure 1, which shows the hyperbolic curve of myoglobin and the sigmoidal transition
