Regulatory control through conformation changes in proteins

Abstract Cooperative effects in proteins such as hemoglobin and feedback enzymes have been observed extensively. A sequential model to explain these effects has been developed in which it is assumed that a ligand can induce a conformational change in an individual subunit and that the distortion in this one subunit may be transmitted with varying efficiencies to neighboring subunits. Expressing these interactions in mathematical form it is found that the models can explain qualitatively and quantitatively a wide variety of phenomena observed in the biological literature. Key features of the model are (a) that there are sequential changes in conformation as ligand is bound, i.e., hybrid conformational states can exist, (b) that the efficiency of transmission of the effect in one subunit to neighboring subunits may vary widely, i.e., the coupling may be very low in which case the protein will exhibit Michaelis-Menten kinetics or it may be very high in which case highly cooperative phenomena will be observed, and (c) that the final conformational state depends on the protein and the ligand bound, i.e., there may be a considerable diversity in the final conformational states with different ligands.