Allosteric Effects, A Big Surprise

The phage display affinity maturation process that focused solely on Sitel produced some unexpected and important consequences in Site2. Sitel and Site2 are on opposite faces of the hormone and are 

The concept that the two spatially distinct binding sites on cytokine hormones are structurally and functionally coupled as displayed in the hGHv complex is novel, and the process whereby new binding surfaces are synthesized by indirect molecule effects has been termed functional cooperativity (Schififer et al., 2002). In this mechanism it is not the mutation(s) in one site that alone affect the other site. A set of concerted 

Biological Implications of Transient Receptor Dimerization 

The role of receptor homodimerization is more complicated than simply bringing the cytoplasmic elements of the receptors together. For example, structural studies of EPO and EPO-R indicate that a function of the hormone is to establish a fairly exact receptor alignment, as well as to induce dimerization (Livnah et al, 1998, 1999 Remy et al, 1999 Wilson and JoUiffe, 1999). Based on patterns of cross-hormone and cross-species activities and the known structural differences in the active complexes, exact receptor orientation is probably not as crucial for prolactin and growth hormone systems, although this has not been directly established. 

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