Interleukin-4 receptor alpha/common gamma chain complex (IL-4R)

The Interleukin-4 receptor alpha/common gamma chain complex, also known as Type I IL-4 receptor, is a heterodimeric transmembrane cytokine receptor. It consists of two subunits: the IL-4 Receptor Alpha Chain (IL-4Rα), which is the ligand-binding subunit with high affinity for IL-4, and the Common Gamma Chain (γc), a lower-affinity subunit shared among multiple cytokine receptors. The IL-4Rα chain binds IL-4 with high affinity, and this intermediate complex subsequently recruits the common gamma chain to initiate transmembrane signaling. The IL-4Rα chain's extracellular binding domain has an L-shaped structure with specific recognition loops and 'hotspot' residues that interact with IL-4, with the ionic interaction between IL-4 Arg-88 and IL-4BP Asp-72 providing most of the binding energy. This complex is a key regulator of immune responses, particularly in allergy and asthma, mediating cell growth, differentiation, and IgE production. It is structurally similar to the IL-2 receptor beta chain and shows homology to the GM-CSF Receptor Complex Chain alpha. Drug development efforts targeting this complex typically focus on the IL-4Rα chain due to its ligand specificity and higher binding affinity.

Other names

IL-4RIL4RIL-4RαType I IL-4 receptorCD124 antigenInterleukin-4 receptor subunit alpha

Drugs targeting the IL-4 receptor alpha/common gamma chain complex would primarily focus on the IL-4Rα chain to prevent IL-4 binding. By blocking the interaction between IL-4 and IL-4Rα, subsequent recruitment of the common gamma chain and initiation of transmembrane signaling would be inhibited. This action aims to disrupt IL-4-mediated immune responses, such as Th2 cell differentiation, IgE production, and macrophage polarization.