Hemoglobin concerted model

Figure 9 Two proposed models for allosteric interaction observed in hemoglobin, (a) A sequential model of allosteric interaction. When one O2 molecule binds to a subunit in the T-state, the subunit shifts to R-state and affects the affinity of neighboring subunits for the ligand binding, (b) An MWC two-state concerted model of allosteric interaction. When one O2 molecule binds to a subunit in all T-states, a concerted conformational change occurs to produce a protein with all R-state subimits. Square and circle represent T- and R-state subunits, respectively. Moreover, opened and closed diagrams represent free and O2 bound subunits, respectively...

What major differences exist between the sequential and concerted models for allostery in accounting for hemoglobin that is partially saturated with oxygen ... 

Sigmoid kinetic behavior generally reflects cooperative interactions between protein subunits. In other words, changes in the structure of one subunit are translated into structural changes in adjacent subunits, an effect mediated by noncovalent interactions at the interface between subunits. The principles are particularly well illustrated by a nonenzyme 02 binding to hemoglobin. Sigmoid kinetic behavior is explained by the concerted and sequential models for subunit interactions (see Fig. 5-15). 

Is the cooperative binding of oxygen by hemoglobin best described by the concerted or the sequential model Neither model in its pure form fully accounts for the behavior of hemoglobin. Instead, a combined model is required. 

It should be emphasized that the concerted and sequential models are theoretical models, that is, the behavior of many allosteric proteins appears to be more complex than can be accounted for by either model. For example, the cooperative binding of Oz by hemoglobin (the most thoroughly researched allosteric protein) appears to exhibit features of both models. The binding of the first 02 initiates a concerted T — R transition that involves small changes in the conformation of each subunit (a feature of the sequential model). In addition, hemoglobin species with only one or two bound 02 have been observed. 

Multistate models Neither the KNF nor the MWC model exactly explains the allosteric behavior of proteins, including hemoglobin. Consequently, more complex models have been devised. Most such models retain the MWC concept of a concerted switch in conformation but involve more than two states for the entire molecule. 

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