Insertion of argos sequences into the B-loop of epidermal growth factor results in a low-affinity ligand with strong agonistic activity

An investigation of the importance of B-loop sequences in determining receptor activation has been conducted. The study also sought to understand their causal role in the antagonistic activity of the Argos ligand. The results showed that a number of nonconservative substitution in the human epidermal growth factor B-loop are tolerated without any effect on receptor binding or activation. They also indicate that both receptor binding and signaling efficiency can be uncoupled, a prerequisite for receptor antagonist development.