Binding of mutant insulins to a mutated insulin receptor

We studied the binding of mutant insulins to both the normal human insulin receptor and an insulin receptor in which the sequence 240-250 of the receptor alpha subunit was mutated to provide an additional net positive charge. One mutant insulin (AspB10), which has an additional negative charge, bound to both types of receptors with a higher affinity than native insulin. Moreover, this mutant insulin was more effective in activating the tyrosine kinase activity of both types of receptors. This study suggests, therefore, that charge interactions between insulin and its receptor may play a role in insulin receptor binding and action.