How peptide hormones that bind to each other co-evolved to build each other's cellular receptors

What is it about?

Dwyer suggested that receptors evolved from self-aggregating peptides, one of which became the ligand, the other the receptor. This paper tests Dwyer's theory with regard to the evolution of the insulin receptor. If Dwyer is right, then the insulin receptor should be composed of modules that are insulin-like. This is, in fact, the case. Moreover, glucose is known to bind to insulin, suggesting that these insulin-like regions of the insulin receptor should also act as glucose binding sites. This prediction is verified, suggesting a mechanism by which the insulin receptor can act as a glucose monitor to help cells regulate their sugar intake.

Featured Image

Why is it important?

The findings in this paper are important for two reasons. First, they validate Dwyer's general theory of how peptide receptors evolved providing the first clear evidence that receptors are made up of repeating modules. This model may explain the structure-function relationships inherent in other ligand-receptor pairs and how they co-evolved. Secondly, it has long been thought that the insulin receptor acts as a glucose sensor to help regulate cellular glucose levels but until now, no mechanism was known. This paper demonstrates that insulin-like regions of the insulin receptor directly bind glucose and that this binding alters the affinity of the insulin receptor for insulin itself. Thus, there is a direct mechanism by which glucose concentrations can modify insulin activity.

Perspectives