Mechanism of cooperativity

How has evolution achieved this miracle of adaptation? As already mentioned the key is cross-talk between binding sites of haemoglobin. Each binding site can occur in a low affinity state (called the "tense" or T state) or in a high affinity ("relaxed" or R) state.

The names "tense" and "relaxed" where originally chosen because in the T-state haemoglobin molecules are stabilised by additional ionic bonds between the a- and ^-subunits, which do not exist in the R-state. The reason is that in the absence of oxygen the haem iron is pulled towards the proximal His, putting a strain on the haem molecule that results in a movement of the surrounding protein helices. Oxygen binding releases this strain.

If there are no oxygen molecules bound to haemoglobin, all 4 subunits will be in the T state, and their affinity to oxygen will be low.

If all 4 subunit have oxygen bound, then all will be in the R state and have a high affinity for oxygen.

You can already see how this works: With low oxygen saturation (in tissue) affinity will be low, and haemoglobin will tend to release oxygen completely. With high oxygen saturation (in the lungs) haemoglobin will have high affinity, and tend to bind as much oxygen as possible — just what is functionally required.

The interesting question is: What happens at intermediate oxygen pressures, how is the transition between all-T and all-S achieved? There are two models for this, the concerted model of J. Monod et al. [54] and the sequential model suggested by D. Koshland et al. [44] (see fig. 7.4).

all tense

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