Structure of the complete extracellular domain of the common β subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration

The receptor systems for the hemopoietic cytokines GM-CSF, IL-3, and IL-5 consist of ligand-specific α receptor subunits that play an essential role in the activation of the shared βc subunit, the major signaling entity. Here, we report the structure of the complete βc extracellular domain. It has a structure unlike any class I cytokine receptor described thus far, forming a stable interlocking dimer in the absence of ligand in which the G strand of domain 1 hydrogen bonds into the corresponding β sheet of domain 3 of the dimer-related molecule. The G strand of domain 3 similarly partners with the dimer-related domain 1. The structure provides new insights into receptor activation by the respective α receptor:ligand complexes.